Role of INPP4B in the proliferation, migration, invasion, and survival of human endometrial cancer cells
Jing Zhao1, Xue-mei Du2, Wen Si1, Xian-he Zhao3 and Zi-qi Zhou3
1Department of Oncology, 2Department of Pathology, Beijing Shijitan Hospital, Capital Medical University and 3Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
Corresponding Author: Jing Zhao, Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, 100038, 10 Tieyi Road, Yangfangdian, Haidian District, Beijing, China. e-mail: zhaojingzj@21cn.com
Summary. Background. Inositol polyphosphate 4-phosphatase type II (INPP4B) has been identified as a tumor repressor in several human cancers while its role in endometrial cancer has not been investigated yet. Therefore, the current study was designed to determine whether INPP4B participates in the progression of endometrial cancer by utilizing clinical data and experimental determination.
Materials and methods. We first include six chemotherapy-treated patients with recurrent and metastatic endometrioid carcinoma to determine the relationship between INPP4B mutation and relative tumor burden. By using siRNA-mediated gene silencing and vector-mediated gene overexpression, we further determined the effect of manipulating INPP4B expression on the proliferation, invasion, and survival of endometrial cancer cells. Furthermore, the repressing effect of INPP4B together with its role in chemotherapy was further validated by xenograft tumor-bearing mice models. Western blot analysis was used to explore further downstream signaling modulated by INPP4B expression manipulation.
Results. Two of the patients were found to have INPP4B mutations and the mutation frequency of INPP4B increased during the progression of chemotherapy resistance. Endometrial cancer cells with silenced INPP4B expression were found to have promoted tumor cell proliferation, invasion, and survival. Endometrial cancer cells overexpressing INPP4B were found to have decreased tumor cell proliferation, invasion, and survival. An in vivo study using six xenograft tumor-bearing mice in each group revealed that INPP4B overexpression could suppress tumor progression and enhance chemosensitivity. Furthermore, INPP4B overexpression was found to modulate the activation of Wnt3a signaling.
Conclusion. The current study suggested that INPP4B could be a suppressor in endometrial cancer progression and might be a target for endometrial cancer treatment. Also, INPP4B might serve as a predictor of chemosensitivity determination. Histol Histopathol
Key words: INPP4B, Endometrial cancer, Wnt3a, Chemosensitivity
DOI: 10.14670/HH-18-711
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©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
