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Distinct regulation of ASCL1 by the cell cycle and chemotherapy in small cell lung cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2024-03-21 Yuning Liu, Qingzhe Wu, Bin Jiang, Tingting Hou, Chuanqiang Wu, Ming Wu, Hai Song
Small cell lung cancer (SCLC) is an aggressive and lethal malignancy. Achaete-scute homolog 1 (ASCL1) is essential for the initiation of SCLC in mice and the development of pulmonary neuroendocrine cells (PNECs) which are the major cells of origin for SCLC. However, the regulatory mechanism of ASCL1 in SCLC remains elusive. Here, we found that ASCL1 expression gradually increases as the tumors grow
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Vasorin exocytosed from glioma cells facilitates angiogenesis via VEGFR2/AKT signaling pathway Mol. Cancer Res. (IF 5.2) Pub Date : 2024-03-15 Ying Zhong, Hui Kang, Ziqing Ma, Jiayu Li, Zixi Qin, Zixuan Zhang, Peiwen Li, Ying Zhong, Lihui Wang
Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial
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LncRNA JPX promotes tumor progression by interacting with and destabilizing YTHDF2 in cutaneous melanoma Mol. Cancer Res. (IF 5.2) Pub Date : 2024-03-05 Dan Luo, Hui Tang, Liuchang Tan, Long Zhang, Lei Wang, Qionghui Cheng, Xia Lei, Jinjin Wu
Aberrant long noncoding RNAs just proximal to Xist (lncRNA JPX) expression levels have been detected in multiple tumors. However, whether JPX is involved in melanoma progression remains unclear. Our study showed that JPX expression is significantly increased in melanoma tissues and cell lines. To clarify the effect of JPX on cutaneous melanoma, we successfully generated JPX-overexpressing or JPX-knockdown
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Low- and high-grade glioma-associated vascular cells differentially regulate tumor growth Mol. Cancer Res. (IF 5.2) Pub Date : 2024-03-05 Sree Deepthi Muthukrishnan, Haocheng Qi, David Wang, Lubayna Elahi, Amy Pham, Alvaro G. Alvarado, Tie Li, Fuying Gao, Riki Kawaguchi, Albert Lai, Harley I. Kornblum
A key feature distinguishing high-grade glioma (HG) from low-grade glioma (LG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor-associated vasculature from HG is molecularly and functionally distinct from normal brain vasculature and expresses higher levels of pro-tumorigenic factors that promote glioma growth and progression. However, it remains
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Systematic characterization of p53-regulated long non-coding RNAs across human cancers reveals remarkable heterogeneity among different tumor types Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-23 Kausik Regunath, Vitalay Fomin, Pingzhang Wang, Zhaoqi Liu, Mainul Hoque, Bin Tian, Raul Rabadan, Carol Prives
The p53 tumor suppressor protein, a sequence specific DNA binding transcription factor, regulates the expression of a large number of genes, in response to various forms of cellular stress. While the protein coding target genes of p53 have been well studied, less is known about its role in regulating long non-coding genes and their functional relevance to cancer. Here we report the genome-wide identification
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Surgical tumour resection deregulates Hallmarks of Cancer in resected tissue and the surrounding microenvironment Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-23 Rohan Chaubal, Nilesh Gardi, Shalaka Joshi, Gouri Pantvaidya, Rasika Kadam, Vaibhav Vanmali, Rohini Hawaldar, Elizabeth Talker, Jaya Chitra, Poonam Gera, Dimple Bhatia, Prajakta Kalkar, Mamta Gurav, Omshree Shetty, Sangeeta Desai, Neeraja M. Krishnan, Nita Nair, Vani Parmar, Amit Dutt, Binay Panda, Sudeep Gupta, Rajendra Badwe
Surgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissue from breast (BRC) (n=81) and head/neck squamous cancer (HNSC) patients (n=10) at the beginning (A), during (B) and end of surgery (C). Tumor/normal RNA from 46/81 breast cancer
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Serotonin receptor HTR2B facilitates colorectal cancer metastasis via CREB1-ZEB1 axis mediated epithelial-mesenchymal transition Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-21 Tao Li, Lei Wei, Xin Zhang, Bin Fu, Yunjiang Zhou, Mengdi Yang, Mengran Cao, Yaxin Chen, Yingying Tan, Yongwei Shi, Leyin Wu, Chenyuan Xuan, Qianming Du, Rong Hu
A number of neurotransmitters have been detected in tumor microenvironment and proved to modulate cancer oncogenesis and progression. We previously found that biosynthesis and secretion of neurotransmitter 5-hydroxytryptamine (5-HT) was elevated in colorectal cancer (CRC) cells. In this study, we discovered that the HTR2B receptor of 5-HT was highly expressed in CRC tumor tissues, which was further
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FATP5 is indispensable for the growth of intrahepatic cholangiocarcinoma Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-15 Diyala Shihadih, Xue Wang, Peter-James H. Zushin, Pavlo Khodakivskyi, Hyo Min Park, Emily Tso, Jena Shiblak, Angela Misic, Sharon M. Louie, Catherine Ward, Marc Hellerstein, Daniel K. Nomura, Elena Goun, Francesco Urigo, Diego F. Calvisi, Xin Chen, Andreas Stahl
Altered lipid metabolism is a common hallmark of various cancers, including Intrahepatic Cholangiocarcinoma (ICC), a highly lethal carcinoma that lacks effective treatment options. To elucidate the lipid metabolism changes in ICC, we coupled the expression of the firefly luciferase gene (FFL) to AKT1 (AKT-FFL) via an IRES linker, and then hydrodynamically injected mice with AKT-FFL and Notch1 intracellular
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SCUBE3 exerts a tumor-promoting effect in tongue squamous cell carcinoma by promoting CEBPA binding to the CCL2 promoter Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-13 Minhui Zhu, Yi Ma, Wei Wang, Meng Li, Shicai Chen, Fei Liu, Xiaoqiong Shi, Hongsen Bi, Chen Zhang, Fangfei Nie, Hongliang Zheng, Caiyun Zhang
Tongue squamous cell carcinoma (TSCC) is the main pathological subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed
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Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-12 Zoi E. Sychev, Abderrahman Day, Hannah E. Bergom, Gabrianne Larson, Atef Ali, Megan Ludwig, Ella Boytim, Ilsa Coleman, Eva Corey, Stephen R. Plymate, Peter S. Nelson, Justin H. Hwang, Justin M. Drake
Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains key features of the
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ROR2/Wnt5a signaling regulates directional cell migration and early tumor cell invasion in ovarian cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-09 Whitney R. Grither, Breanna Baker, Vasilios A. Morikis, Ma. Xenia G. Ilagan, Katherine C. Fuh, Gregory D. Longmore
Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate non-canonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular
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Co-regulation of NDC80 complex subunits determines the fidelity of the spindle-assembly checkpoint and mitosis Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-07 Se Hong Kim, Thomas T.Y. Lau, Man Kit Liao, Hoi Tang Ma, Randy Y.C. Poon
NDC80 complex (NDC80C) is composed of four subunits (SPC24, SPC25, NDC80, and NUF2) and is vital for kinetochore–microtubule (KT–MT) attachment during mitosis. Paradoxically, NDC80C also functions in the activation of the spindle-assembly checkpoint (SAC). This raises an interesting question regarding how mitosis is regulated when NDC80C levels are compromised. Using a degron-mediated depletion system
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Oncogenic GNAS uses PKA-dependent and independent mechanisms to induce cell proliferation in human pancreatic ductal and acinar organoids Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-06 Ridhdhi Desai, Ling Huang, Raul S. Gonzalez, Senthil K. Muthuswamy
Ductal and acinar pancreatic organoids are promising models for the study of pancreatic diseases. Genome sequencing studies have revealed that mutations in a G-protein (GNASR201C) are exclusively observed in intraductal papillary mucinous neoplasms (IPMNs). The biological mechanisms by which GNASR201C affects the ductal and acinar exocrine pancreas are unclear. Here, we use human stem-cell-derived
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An endosomal acid-regulatory feedback system rewires cytosolic cAMP metabolism and drives tumour progression Mol. Cancer Res. (IF 5.2) Pub Date : 2024-02-06 Hari Prasad, Susmita Mandal, John Kandam Kulathu Mathew, Aparna Cherukunnath, Atchuta Srinivas Duddu, Mallar Banerjee, Harini Ramani, Ramray Bhat, Mohit Kumar Jolly, Sandhya S. Visweswariah
Although suppressed cAMP levels have been linked to cancer for nearly five decades, the molecular basis remains uncertain. Here, we identify endosomal pH as a novel regulator of cytosolic cAMP homeostasis and a promoter of transformed phenotypic traits in colorectal cancer (CRC). Combining experiments and computational analysis, we show that the Na+/H+ exchanger NHE9 contributes to proton leak and
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NRAS mutant dictates AHCYL1-governed ER calcium homeostasis for melanoma tumor growth Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-31 Chufan Cai, Jiayi Tu, Jeronimo Najarro, Rukang Zhang, Hao Fan, Freya Q. Zhang, Jiacheng Li, Zhicheng Xie, Rui Su, Lei Dong, Nicole Arellano, Michele Ciboddo, Shannon E. Elf, Xue Gao, Jing Chen, Rong Wu
Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1),
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Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-29 Mohamed Omar, Zhuoran Xu, Sophie B. Rand, Mohammad K. Alexanderani, Daniela C. Salles, Itzel Valencia, Edward M. Schaeffer, Brian D. Robinson, Tamara L. Lotan, Massimo Loda, Luigi Marchionni
Prostate cancer (PCa) harbors several genetic alterations, the most prevalent of which is TMPRSS2:ERG gene fusion, affecting nearly half of all cases. Capitalizing on the increasing availability of whole-slide images (WSIs), this study introduces a deep learning (DL) model designed to detect TMPRSS2:ERG fusion from H&E-stained WSIs of radical prostatectomy specimens. Leveraging the TCGA prostate adenocarcinoma
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AIbZIP/CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple Negative Breast Cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-18 Taichi Ito, Atsushi Saito, Yasunao Kamikawa, Nayuta Nakazawa, Kazunori Imaizumi
Breast cancer ranks first in incidence and fifth in cancer-related deaths among all types of cancer globally. Among breast cancer, triple negative breast cancer (TNBC) has few known therapeutic targets and a poor prognosis. Therefore, new therapeutic targets and strategies against TNBC are required. We found that androgen-induced basic leucine zipper (AIbZIP) [also known as cyclic AMP–responsive element-binding
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miR-217 regulates normal and tumor cell fate following induction of Endoplasmic Reticulum Stress Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-18 Neekkan Dey, Constantinos Koumenis, Davide Ruggero, Serge Y. Fuchs, J. Alan Diehl
Rapidly proliferating cancer cells must thrive in a microenvironment wherein metabolic nutrients such as glucose, oxygen and growth factors become limiting as tumor volume expands beyond the established vascularity of the tissue. Limits in nutrient availability typically trigger growth arrest and/or apoptosis to prevent cellular expansion. However, tumor cells frequently co-opt cellular survival pathways
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Mass spectrometry-based proteomics identifies Serpin B9 as a key protein in promoting bone metastases in lung cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-16 Yufeng Huang, Ming Gong, Hongmin Chen, Chuangzhong Deng, Xiaojun Zhu, Jiaming Lin, Anfei Huang, Yanyang Xu, Yi Tai, Guohui Song, Huaiyuan Xu, Jinxin Hu, Huixiong Feng, Qinglian Tang, Jinchang Lu, Jin Wang
Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based
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Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-16 Vinay K. Pattalachinti, Ichiaki Ito, Saikat Chowdhury, Abdelrahman Yousef, Yue Gu, Betul Beyza Gunes, Emma R. Salle, Melissa Taggart, Keith Fournier, Natalie W. Fowlkes, John Paul Shen
Appendiceal Adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDXs) to study the effect of the peritoneal
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LRRC75A-AS1 drives the epithelial-mesenchymal transition in cervical cancer by binding IGF2BP1 and inhibiting SYVN1-mediated NLRP3 ubiquitination Mol. Cancer Res. (IF 5.2) Pub Date : 2024-01-05 Hongying Sui, Caixia Shi, Zhipeng Yan, Jinyang Chen, Lin Man, Fang Wang
Cervical cancer severely affects women’s health with increased incidence and poor survival for patients with metastasis. Our study aims to investigate the mechanism by which lncRNA LRRC75A-AS1 regulates the epithelial-mesenchymal transition (EMT) of cervical cancer through modulating m6A and ubiquitination modification. In this study, tumor tissues were collected from patients to analyze the expression
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Identification of colorectal cancer cell stemness from single-cell RNA sequencing Mol. Cancer Res. (IF 5.2) Pub Date : 2023-12-29 Kangyu Lin, Saikat Chowdhury, Mohammad A. Zeineddine, Fadl A. Zeineddine, Nicholas J. Hornstein, Oscar E. Villarreal, Dipen M. Maru, Cara L. Haymaker, Jean-Nicolas Vauthey, George J. Chang, Elena Bogatenkova, David Menter, Scott Kopetz, John Paul Shen
Cancer stem cells (CSCs) play a critical role in metastasis, relapse, and therapy resistance in colorectal cancer. While characterization of the normal lineage of cell development in the intestine has led to the identification of many genes involved in the induction and maintenance of pluripotency, recent studies suggest significant heterogeneity in CSC populations. Moreover, while many canonical colorectal
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FGFR1 signaling facilitates obesity-driven pulmonary outgrowth in metastatic breast cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2023-12-28 Eylem Kulkoyluoglu Cotul, Muhammad Hassan Safdar, Sebastian Juan Paez, Aneesha Kulkarni, Mitchell G. Ayers, Hang Lin, Zilin Xianyu, Dorothy Teegarden, Stephen D. Hursting, Michael K. Wendt
Survival of dormant, disseminated breast cancer (BC) cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk of developing metastatic recurrence. Herein, we investigated the effect of diet-induced obesity (DIO) on primary tumor growth and metastatic progression using both metastatic and systemically dormant mouse models of BC. This approach
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Mitochondria transfer by platelet-derived microparticles regulates breast cancer bioenergetic states and malignant features Mol. Cancer Res. (IF 5.2) Pub Date : 2023-12-12 Vanessa Veilleux, Nicolas Pichaud, Luc H. Boudreau, Gilles A. Robichaud
An increasing number of studies show that platelets as well as platelet-derived microparticles (PMPs) play significant roles in cancer malignancy and disease progression. Particularly, PMPs have the capacity to interact and internalize within target cells resulting in the transfer of their bioactive cargo, which can modulate the signaling and activation processes of recipient cells. We recently identified
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Single-cell transcriptomics reveals pre-existing COVID-19 vulnerability factors in lung cancer patients Mol. Cancer Res. (IF 5.2) Pub Date : 2023-12-08 Wendao Liu, Wenbo Li, Zhongming Zhao
COVID-19 and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that cancer patients are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma
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TNFRSF19 within the 13q12.12 risk locus functions as a lung cancer suppressor by binding Wnt3a to inhibit Wnt/β-catenin signaling. Mol. Cancer Res. (IF 5.2) Pub Date : 2023-12-04 Xianglin Zuo, Xuchun Wang, Tingzheng Ma, Shuhan Chen, Pingping Cao, He Cheng, Nan Yang, Xiao Han, Wei Gao, Xiaoyu Liu, Yujie Sun
Cancer risk loci provide especial clues for uncovering pathogenesis of cancers. The TNFRSF19 gene located within the 13q12.12 lung cancer risk locus encodes tumor necrosis receptor superfamily 19 (TNFRSF19) protein and has been proved to be a key target gene of a lung tissue-specific tumor suppressive enhancer, but its functional role in lung cancer pathogenesis remains to be elucidated. Here we showed
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Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton’s Tyrosine Kinase Mol. Cancer Res. (IF 5.2) Pub Date : 2023-11-28 Himanshu Savardekar, Carter Allen, Hyeongseon Jeon, Jianying Li, Dionisia Quiroga, Emily Schwarz, Richard C. Wu, Sara Zelinskas, Gabriella Lapurga, Alexander Abreo, Andrew Stiff, Jami Shaffer, Bradley W. Blaser, Matthew Old, Robert Wesolowski, Gang Xin, Kari L. Kendra, Dongjun Chung, William E. Carson
Myeloid-derived suppressor cell (MDSC) levels are elevated in cancer patients and contribute to reduced efficacy of immune checkpoint therapy. MDSC express Bruton’s Tyrosine Kinase (BTK) and BTK inhibition with ibrutinib, an FDA-approved irreversible inhibitor of BTK, leads to reduced MDSC expansion/function in mice and significantly improves the anti-tumor activity of anti-PD-1 antibody treatments
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Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice Mol. Cancer Res. (IF 5.2) Pub Date : 2023-11-28 Ivana Barravecchia, Jennifer M. Lee, Jason Manassa, Brian Magnuson, Sarah F. Ferris, Sophia Cavanaugh, Nina G. Steele, Carlos E. Espinoza, Craig J. Galbán, Nithya Ramnath, Timothy L. Frankel, Marina Pasca di Magliano, Stefanie Galban
Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. IPF patients have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated
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LINC00869 promotes hepatocellular carcinoma metastasis via protrusion formation Mol. Cancer Res. (IF 5.2) Pub Date : 2023-11-07 Xiaowen Shao, Yamei Dang, Tingting Zhang, Nan Bai, Jianing Huang, Mengya Guo, Li Sun, Minghe Li, Xiao Sun, Xinran Zhang, Feng Han, Ning Zhang, Hao Zhuang, Yongmei Li
Coordination of filament assembly and membrane remodeling is required for the directional migration of cancer cells. The Wiskott–Aldrich syndrome protein (WASp) recruits the actin-related protein (Arp) 2/3 complex to assemble branched actin networks. The goal of our study was to assess the potential regulatory role exerted by the novel long non-coding RNA (lncRNA) LINC00869 on hepatocellular carcinoma
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ORAOV1, CCND1, and MIR548K are the driver oncogenes of the 11q13 amplicon in squamous cell carcinoma Mol. Cancer Res. (IF 5.2) Pub Date : 2023-11-06 Celine I. Mahieu, Andrew G. Mancini, Ellee P. Vikram, Vicente Planells-Palop, Nancy M. Joseph, Aaron D. Tward
11q13 amplification is a frequent event in human cancer and in particular in squamous cell carcinomas (SCC). Despite almost invariably spanning 10 genes, it is unclear which genetic components of the amplicon are the key driver events in SCC. A combination of computational, in vitro, ex vivo and in vivo models leveraging efficient primary human keratinocyte genome editing by Cas9-RNP electroporation
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The role of the gut microbiome in hematological cancers Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-31 Najihah Hussein, Reena Rajasuriar, Asif M. Khan, Yvonne AI-Lian Lim, Gin Gin Gan
Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome indicate how it may affect human health and disease susceptibility. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of haematological cancers. A variety of mechanisms, including
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PKCð regulates chromatin remodeling and DNA repair through SIRT6 Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-27 Trisiani Affandi, Ami Haas, Angela M. Ohm, Gregory M. Wright, Joshua C. Black, Mary E. Reyland
Irradiation (IR) is a highly effective cancer therapy, however, IR damage to tumor-adjacent healthy tissues can result in significant co-morbidities and potentially limit the course of therapy. We have previously shown that protein kinase C delta (PKCð) is required for IR-induced apoptosis and that inhibition of PKCð activity provides radioprotection in vivo. Here we show that PKCð regulates histone
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Canonical and nuclear mTOR specify distinct transcriptional programs in androgen-dependent prostate cancer cells Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-27 Yonghong Chen, Lingwei Han, Catherine Rosa Dufour, Anthony Alfonso, Vincent Giguere
mTOR is a serine/threonine kinase that controls prostate cancer (PCa) cell growth in part by regulating gene programs associated with metabolic and cell proliferation pathways. mTOR-mediated control of gene expression can be achieved via phosphorylation of transcription factors, leading to changes in their cellular localization and activities. mTOR also directly associates with chromatin in complex
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Exosomal lncRNA NEAT1 inhibits NK cell activity to promote multiple myeloma cell immune escape via an EZH2/PBX1 axis Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-27 Qing-Ming Wang, Guang-Yu Lian, Su-Mei Sheng, Jing Xu, Long-Long Ye, Chao Min, Shu-Fang Guo
Exosomal long noncoding RNAs (lncRNAs) derived from cancer cells are implicated in various processes, including cancer cell proliferation, metastasis, and immunomodulation. We investigated the role and underlying mechanism of exosome-transmitted lncRNA NEAT1 in the immune escape of multiple myeloma (MM) cells from natural killer (NK) cells. MM cells and samples from MM patients were obtained. The effects
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Mitochondrial translocase TOMM22 is overexpressed in pancreatic cancer and promotes aggressive growth by modulating mitochondrial protein import and function Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-25 Mary Oluwadamilola Haastrup, Kunwar Somesh Vikramdeo, Shashi Anand, Mohammad Aslam Khan, James Elliot Carter, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta
Pancreatic cancer has the worst prognosis among all cancers underscoring the need for improved management strategies. Dysregulated mitochondrial function is a common feature in several malignancies, including pancreatic cancer. Although mitochondria have their own genome, most mitochondrial proteins are nuclear-encoded and imported by a multi-subunit translocase of the outer mitochondrial membrane
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Spatial transcriptomics suggests that alterations occur in the preneoplastic breast microenvironment of BRCA1/2 mutation carriers Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-25 Anthony Caputo, Kavya Vipparthi, Peter Bazeley, Erinn Downs-Kelly, Patrick McIntire, Lauren A. Duckworth, Ying Ni, Bo Hu, Ruth A. Keri, Mihriban Karaayvaz
Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like
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Impact of rare and multiple concurrent gene fusions on diagnostic DNA methylation classifier in brain tumors Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-23 Kristyn Galbraith, Jonathan Serrano, Guomiao Shen, Ivy Tran, Cheyanne C. Slocum, Courtney Ketchum, Zied Abdullaev, Rust Turakulov, Tejus Bale, Marc Ladanyi, Purvil Sukhadia, Michael Zaidinski, Kerry Mullaney, Sara DiNapoli, Benjamin L. Liechty, Marissa Barbaro, Jeffrey C. Allen, Sharon L. Gardner, Jeffrey Wisoff, David Harter, Eveline Teresa Hidalgo, John G. Golfinos, Daniel A. Orringer, Kenneth Aldape
DNA methylation is an essential molecular assay for central nervous system tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA NGS. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare
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SOX10 loss sensitizes melanoma cells to cytokine-mediated inflammatory cell death Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-17 Sheera R. Rosenbaum, Signe Caksa, Casey D. Stefanski, Isabella V. Trachtenberg, Haley P. Wilson, Nicole A. Wilski, Connor A. Ott, Timothy J. Purwin, Jelan I. Haj, Danielle Pomante, Daniel Kotas, Inna Chervoneva, Claudia Capparelli, Andrew E. Aplin
The transcription factor, SOX10, plays an important role in the differentiation of neural crest precursors to the melanocytic lineage. Malignant transformation of melanocytes leads to the development of melanoma, and SOX10 promotes melanoma cell proliferation and tumor formation. SOX10 expression in melanomas is heterogeneous, and loss of SOX10 causes a phenotypic switch towards an invasive, mesenchymal-like
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Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-17 Eranga R. Balasooriya, Deshan Madhusanka, Tania P. Lopez-Palacios, Riley J. Eastmond, Dasun Jayatunge, Jake J. Owen, Jack S. Gashler, Christina M. Egbert, Chanaka Bulathsinghalage, Lu Liu, Stephen R. Piccolo, Joshua L. Andersen
Beyond the most common oncogenes activated by mutation (mut-drivers) there likely exists a variety of low-frequency mut-drivers, each of which is a possible frontier for targeted therapy. To identify new and understudied mut-drivers, we developed a machine learning (ML) model that integrates curated clinical cancer data and post-translational modification (PTM) proteomics databases. We applied the
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RNF185 control of COL3A1 expression limits prostate cancer migration and metastatic potential Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-13 Benjamin Van Espen, Htoo Zarni Oo, Colin Collins, Ladan Fazil, Alfredo Molinolo, Kevin Yip, Rabi Murad, Martin Gleave, Ze'ev A. Ronai
RNF185 is a RING finger domain-containing ubiquitin ligase implicated in ER-associated degradation. Prostate tumor patient data analysis revealed a negative correlation between RNF185 expression and prostate cancer progression and metastasis. Likewise, several prostate cancer cell lines exhibited greater migration and invasion capabilities in culture upon RNF185 depletion. Subcutaneous inoculation
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Distinct microRNA signature and suppression of ZFP36L1 define ASCL1-positive lung adenocarcinoma Mol. Cancer Res. (IF 5.2) Pub Date : 2023-10-06 Takayoshi Enokido, Masafumi Horie, Seiko Yoshino, Hiroshi I Suzuki, Rei Matsuki, Hans Brunnström, Patrick Micke, Takahide Nagase, Akira Saito, Naoya Miyashita
Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas and exerts tumor-promoting effects. Here, we explored microRNA (miRNA) profiles in ASCL1-positive lung adenocarcinomas and identified several miRNAs closely associated with ASCL1 expression, including miR-375
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Metabolic hallmarks for purine nucleotide biosynthesis in small-cell lung carcinoma Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-29 Sho Tabata, Shigeki Umemura, Miyu Narita, Hibiki Udagawa, Takamasa Ishikawa, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii, Katsuya Tsuchihara, Atsushi Ochiai, Susumu S. Kobayashi, Tomoyoshi Soga, Hideki Makinoshima
Small-cell lung cancer (SCLC) has a poor prognosis, emphasizing the necessity for developing new therapies. The de novo synthesis pathway of purine nucleotides, which is involved in the malignant growth of SCLC, has emerged as a novel therapeutic target. Purine nucleotides are supplied by two pathways: de novo and salvage. However, the role of the salvage pathway in SCLC and the differences in utilization
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Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-28 Yu-Lin Lin, Jun-Qi Zhu, Rui-Qing Ma, Wei Meng, Zi-Yue Wang, Xin-Bao Li, Ru Ma, He-Liang Wu, Hong-Bin Xu, Ying Gao, Yan Li
Pseudomyxoma peritonei (PMP) is a rare malignant clinical syndrome with little known about the global mutation profile. In this study, whole-exome sequencing (WES) was performed in 49 appendiceal PMP to investigate mutation profiles and mutation signatures. A total of 4020 somatic mutations were detected, with a median mutation number of 56 (1 – 402). Tumor mutation burden (TMB) was generally low (median
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SP4 facilitates esophageal squamous cell carcinoma progression by activating PHF14 transcription and Wnt/β-Catenin signaling Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-28 Li Wei, Chaowei Deng, Bo Zhang, Guanghui Wang, Yan Meng, Hao Qin
Specificity protein 4 transcription factor (SP4), a member of the Sp/Krüppel-like family (KLF), could bind to GT and GC box promoters, and plays an essential role in transcriptional activating. Despite SP4 has been detected to be highly expressed in a variety of human tumors, its biological effect and underlying molecular mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Our research
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PRL2 phosphatase promotes oncogenic KIT signaling in leukemia cells through modulating CBL phosphorylation Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-27 Hongxia Chen, Yunpeng Bai, Michihiro Kobayashi, Shiyu Xiao, Sergio Barajas, Wenjie Cai, Sisi Chen, Jinmin Miao, Frederick Nguele Meke, Chonghua Yao, Yuxia Yang, Katherine Strube, Odelia Satchivi, Jianmin Sun, Lars Ronnstrand, James M. Croop, H Scott Boswell, Yuzhi Jia, Huiping Liu, Loretta S. Li, Jessica K. Altman, Elizabeth A. Eklund, Madina Sukhanova, Peng Ji, Wei Tong, Hamid Band, Danny T. Huang
Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT
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AACR Cancer Centers Alliance: Fostering Collaboration and Innovation to Advance Lifesaving Scientific Discoveries for Patients Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-21 Carlos L. Arteaga, John L. Cleveland, Margaret Foti, Ruben A. Mesa, Louis M. Weiner, Cheryl L. Willman, David A. Tuveson
Basic and clinical cancer research discoveries stemming from the nation's cancer centers have markedly improved outcomes for many cancer patients. Despite this forward momentum in our progress against this complex disease, cancer in all its forms remains a major public health challenge that touches the lives of nearly every American, either directly or indirectly. The newly formed AACR Cancer Centers
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Neo-Darwinian Principles Exemplified in Cancer Genomics Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-18 Karl E. Krueger
Within the last two decades the advent of next generation sequencing accompanied by single-cell technologies has enabled cancer researchers to study in detail mutations and other genetic aberrations that transpire during transformation of cells to a neoplastic state. This article covers the insights gained through these extensive studies where neo-Darwinian principles can be inferred to play roles
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BACH1 Loss Exerts Antitumor Effects on Mantle Cell Lymphoma Cells via Inducing a Tumor-Intrinsic Innate Immune Response and Cell-Cycle Arrest Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-15 Guilan Li, Min Feng, Ziting Zhang, Jiangyuan Liu, Han Zhang
BTB and CNC homology 1 (BACH1) is a transcription repressor that regulates multiple physiological processes, including intracellular heme homeostasis and immune responses. Increasing lines of evidence indicate that BACH1 reshapes metastasis and metabolism of human solid tumors. However, its potential roles in mantle cell lymphoma (MCL) remain largely unknown. Here, we found that silencing BACH1 in
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Early immune changes support signet ring cell dormancy in CDH1-driven hereditary diffuse gastric carcinogenesis Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-14 Benjamin L. Green, Lauren A. Gamble, Laurence P. Diggs, Darryl Nousome, Jesse C. Patterson, Brian A. Joughin, Billel Gasmi, Stephanie C. Lux, Sarah G. Samaranayake, Markku Miettinen, Martha Quezado, Jonathan M. Hernandez, Michael B. Yaffe, Jeremy L. Davis
Stage IA gastric adenocarcinoma, characterized by foci of intramucosal signet ring cells (SRCs), is found in nearly all asymptomatic patients with germline pathogenic CDH1 variants and hereditary diffuse gastric cancer syndrome (HDGC). The molecular steps involved in initiating malignant transformation and promoting SRC dormancy in HDGC are unknown. Here, whole-exome bulk RNA sequencing (RNAseq) of
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Interleukin-6 Facilitates Acute Myeloid Leukemia Chemoresistance via Mitofusin 1–Mediated Mitochondrial Fusion Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-12 Diyu Hou, Xiaoming Zheng, Danni Cai, Ruolan You, Jingru Liu, Xiaoting Wang, Xinai Liao, Maoqing Tan, Liyan Lin, Jin Wang, Shuxia Zhang, Huifang Huang
Acute myeloid leukemia (AML), an aggressive hematopoietic malignancy, exhibits poor prognosis and a high recurrence rate largely because of primary and secondary drug resistance. Elevated serum IL6 levels have been observed in patients with AML and are associated with chemoresistance. Chemoresistant AML cells are highly dependent on oxidative phosphorylation (OXPHOS), and mitochondrial network remodeling
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The androgen receptor does not directly regulate the transcription of DNA damage response genes. Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-12 Sylwia Hasterok, Thomas G. Scott, Devin G. Roller, Adam Spencer, Arun B. Dutta, Kizhakke M. Sathyan, Daniel E. Frigo, Michael J. Guertin, Daniel Gioeli
The clinical success of combined androgen deprivation therapy (ADT) and radiation therapy (RT) in prostate cancer (PCa) created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription
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AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells Mol. Cancer Res. (IF 5.2) Pub Date : 2023-09-08 Guangyan Sun, Guy J. Leclerc, Sanjay Chahar, Julio C. Barredo
The survival rates for relapsed/refractory acute lymphoblastic leukemia (ALL) remain poor. We and others have reported that ALL cells are vulnerable to conditions inducing energy/ER-stress mediated by AMP-activated protein kinase (AMPK). To identify the target genes directly regulated by AMPKα2, we performed genome-wide RNA-seq and ChIP-seq in CCRF-CEM (T-ALL) cells expressing HA-AMPKα2 (CN2) under
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m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-30 Zhe Kong, Yali Lu, Yue Yang, Kun Chang, Yan Lin, Yan Huang, Chenji Wang, Lu Zhang, Wei Xu, Shimin Zhao, Yao Li
The pathologic significance of the circular RNA DDIT4 (circDDIT4), which is formed by backsplicing at the 3′-untranslated region (UTR) with a 5′ splice acceptor site in exon 2 of linear DDIT4 mRNA, has yet to be determined. Our study found that circDDIT4 is downregulated in prostate cancer and functions as a tumor suppressor during prostate cancer progression. By competitively binding to ELAV-like
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Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110β-PAK1 in Castration-resistant Prostate Cancer Invasion Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-22 Haizhen Wang, Yu Zhou, Chen Chu, Jialing Xiao, Shanshan Zheng, Manav Korpal, Joshua M. Korn, Tiffany Penaloza, Richard R. Drake, Wenjian Gan, Xueliang Gao
Although androgen deprivation treatment often effectively decreases prostate cancer, incurable metastatic castration-resistant prostate cancer (CRPC) eventually occurs. It is important to understand how CRPC metastasis progresses, which is not clearly defined. The loss of PTEN, a phosphatase to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate in the PI3K pathway, occurs in up to 70% to 80%
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Competing Engagement of β-arrestin Isoforms Balances IGF1R/p53 Signaling and Controls Melanoma Cell Chemotherapeutic Responsiveness Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-16 Sonia Cismas, Sylvya Pasca, Caitrin Crudden, Iara Trocoli Drakensjo, Naida Suleymanova, Simin Zhang, Benjamin Gebhard, Dawei Song, Shiyong Neo, Takashi Shibano, Terry J. Smith, George A. Calin, Ada Girnita, Leonard Girnita
Constraints on the p53 tumor suppressor pathway have long been associated with the progression, therapeutic resistance, and poor prognosis of melanoma, the most aggressive form of skin cancer. Likewise, the insulin-like growth factor type 1 receptor (IGF1R) is recognized as an essential coordinator of transformation, proliferation, survival, and migration of melanoma cells. Given that β-arrestin (β-arr)
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FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-04 Bo Dong, Xiang Song, Xinzhao Wang, Tao Dai, Jianlin Wang, Zhiyong Yu, Jiong Deng, B. Mark Evers, Yadi Wu
Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function
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Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-01 Hui-Hsuan Lin, Chiu-Yuan Chang, Yi-Ren Huang, Che-Hung Shen, Yu-Chen Wu, Kai-Li Chang, Yueh-Chun Lee, Ya-Chi Lin, Wen-Chien Ting, Han-Ju Chien, Yi-Feng Zheng, Chien-Chen Lai, Kuei-Yang Hsiao
Evidence that circular RNAs (circRNA) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here, we show that the presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating
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Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins Mol. Cancer Res. (IF 5.2) Pub Date : 2023-08-01 Angela M. Schab, Molly M. Greenwade, Elizabeth Stock, Elena Lomonosova, Kevin Cho, Whitney R. Grither, Hollie Noia, Daniel Wilke, Mary M. Mullen, Andrea R. Hagemann, Ian S. Hagemann, Premal H. Thaker, Lindsay M. Kuroki, Carolyn K. McCourt, Dineo Khabele, Matthew A. Powell, David G. Mutch, Peinan Zhao, Leah P. Shriver, Gary J. Patti, Gregory D. Longmore, Katherine C. Fuh
Ovarian cancer is the leading cause of gynecologic cancer–related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression
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CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer Mol. Cancer Res. (IF 5.2) Pub Date : 2023-07-26 Lyla J. Stanland, Hazel X. Ang, Jacob P. Hoj, Yunqiang Chu, Patrick Tan, Kris C. Wood, Micah A. Luftig
PIK3CA is the second most mutated gene in cancer leading to aberrant PI3K/AKT/mTOR signaling and increased translation, proliferation, and survival. Some 4%–25% of gastric cancers display activating PIK3CA mutations, including 80% of Epstein–Barr virus–associated GCs. Small molecules, including pan-PI3K and dual PI3K/mTOR inhibitors, have shown moderate success clinically, due to broad on-target/off-tissue
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Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma Mol. Cancer Res. (IF 5.2) Pub Date : 2023-07-26 Masahiro Shinada, Daiki Kato, Tomoki Motegi, Masaya Tsuboi, Namiko Ikeda, Susumu Aoki, Takaaki Iguchi, Toshio Li, Yuka Kodera, Ryosuke Ota, Yuko Hashimoto, Yosuke Takahashi, James Chambers, Kazuyuki Uchida, Yukinari Kato, Ryohei Nishimura, Takayuki Nakagawa
Mucosal melanoma metastasizes at an early stage of the disease in human and dog. We revealed that overexpression of podoplanin in tumor invasion fronts (IF) was related to poor prognosis of dogs with mucosal melanoma. Moreover, podoplanin expressed in canine mucosal melanoma cells promotes proliferation and aggressive amoeboid invasion by activating Rho-associated kinase (ROCK)-myosin light chain 2