KIN17 promotes tumor metastasis by activating EMT signaling in luminal ‐A breast cancer
Autor: | Qiyuan Huang, Hongling Huang, Jingxin Yin, Jinsi Chen, Xiangxiong Pang, Umar Raza, Meifeng Zhong, Kashif Rafiq Zahid, Tao Zeng, Jiamin Zeng, Xinhong Zhu, Weifeng Pan |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Epithelial-Mesenchymal Transition Breast Neoplasms migration medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer In vivo Cell Line Tumor Biomarkers Tumor medicine metastasis Humans Neoplasm Invasiveness Neoplasm Metastasis KIN17 Lung cancer RC254-282 Matrigel Gene knockdown business.industry EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens Lum‐A breast cancer RNA-Binding Proteins Cancer Original Articles General Medicine medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology 030220 oncology & carcinogenesis MCF-7 Cells Cancer research Original Article Carcinogenesis business |
Zdroj: | Thoracic Cancer Thoracic Cancer, Vol 12, Iss 13, Pp 2013-2023 (2021) |
ISSN: | 1759-7714 1759-7706 |
DOI: | 10.1111/1759-7714.14004 |
Popis: | 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. KIN17 expression is associated with poor overall survival (OS), relapse‐free survival (RFS), distant metastasis‐free survival (DMFS) and post‐progression survival (PPS), particularly in luminal‐A breast cancer patients. KIN17 knockdown inhibits whereas its overexpression promotes migration and invasion of MCF‐7 cells via regulating EMT‐associated signaling pathways in vitro and in vivo. |
Databáze: | OpenAIRE |
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