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YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/β-catenin signaling axis

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Abstract

Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/β-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/β-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was partially supported by grants from the National Natural Science Foundation of China (82173063), Wuxi Taihu Lake Talent Plan for Leading Talents in Medical and Health Profession, and Wuxi Medical Key Discipline (ZDXK2021002).

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Authors and Affiliations

  1. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, 214062, Jiangsu, China

    Yuanben Wang, Yulin Cao, Ying Chen, Han Cheng, Zhiang Liu, Mengna Wang, Kaisa Cui & Zhaohui Huang

  2. Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China

    Yuanben Wang, Yulin Cao, Ying Chen, Han Cheng, Zhiang Liu, Mengna Wang, Yuyang Feng, Kaisa Cui & Zhaohui Huang

  3. Department of Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, 1000 He Feng Road, Wuxi, 214122, Jiangsu, China

    Bojian Fei

Authors
  1. Yuanben Wang
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  2. Yulin Cao
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  3. Ying Chen
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  4. Han Cheng
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Contributions

ZHH conceived and designed the project. YBW, YLC, YC, HC, and ZAL performed all experiments. KSC, YBW, YLC, and MNW performed the statistical analyses. YYF and BJF were responsible for clinical sample collection. ZHH, KSC, and YBW prepared, wrote, and/or revised the paper. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Zhaohui Huang.

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The authors declare that they have no competing interests.

Ethical approval

The present study was approved by the Clinical Research Ethics Committees of the participating institutions.

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Wang, Y., Cao, Y., Chen, Y. et al. YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/β-catenin signaling axis. Med Oncol 41, 100 (2024). https://doi.org/10.1007/s12032-024-02349-x

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