KIN17 promotes tumor metastasis by activating EMT signaling in luminal‐A breast cancer

Autor: Qiyuan Huang, Kashif Rafiq Zahid, Jinsi Chen, Xiangxiong Pang, Meifeng Zhong, Hongling Huang, Weifeng Pan, Jingxin Yin, Umar Raza, Jiamin Zeng, Xinhong Zhu, Tao Zeng
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Thoracic Cancer, Vol 12, Iss 13, Pp 2013-2023 (2021)
Druh dokumentu: article
ISSN: 1759-7714
1759-7706
DOI: 10.1111/1759-7714.14004
Popis: Abstract Background Breast cancer (BC), the most common cause of cancer death in women, overtook lung cancer as the leading cause of cancer worldwide in 2020. Although many studies have proposed KIN17 as a biomarker of tumorigenesis in different cancer types, its role in tumor metastasis, particularly in BC metastasis, has been underexplored. This study aimed to explore the role of KIN17 in BC metastasis. Methods Survival analyses was performed to identify the association between KIN17 expression and BC patient survival in silico. Using lentivirus constructs, we developed bidirectional KIN17 expression (KD, knockdown; OE, overexpression) cellular models of luminal‐A (Lum‐A) breast cancer MCF‐7 cells. We performed in vitro wound healing, transwell with and without Matrigel assays, and in vivo tail‐vein metastasis assay to evaluate the migration and invasion abilities of MCF‐7 with stable KIN17 knockdown or overexpression. Western blotting was performed to compare the changes in protein expression. Results We found that KIN17 expression was associated with poor overall survival (OS), relapse‐free survival (RFS), distant metastasis‐free survival (DMFS) and post‐progression survival (PPS), particularly in Lum‐A breast cancer patients. Later, we found that KIN17 knockdown inhibited migration and invasion of MCF‐7 cells via regulating EMT‐associated signaling pathways in vitro and decreases metastatic spread of the disease in vivo. In contrast, KIN17 overexpression promoted migration and invasion of MCF‐7 cells in vitro and increased the metastatic spread of the disease in vivo. Conclusions Overall, our findings provide preliminary data which suggests KIN17 of importance to target in metastatic Lum‐A patients.
Databáze: Directory of Open Access Journals
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