Integrin β4 promotes DNA damage-related drug resistance in triple-negative breast cancer via TNFAIP2/IQGAP1/RAC1
Huan Fang,
Wenlong Ren,
Qiuxia Cui,
Huichun Liang,
Chuanyu Yang,
Wenjing Liu,
Xinye Wang,
Xue Liu,
Yujie Shi,
Jing Feng,
Ceshi Chen
Affiliations
Huan Fang
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, Yunnan, China
Wenlong Ren
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; School of Life Science, University of Science & Technology of China, Hefei, China
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Affiliated Hospital of Guangdong Medical University, Guangdong, China; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
Huichun Liang
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
Chuanyu Yang
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
Wenjing Liu
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
Xinye Wang
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
Xue Liu
Shanghai University of Medicine & Health Sciences Affiliated Sixth People’s Hospital South Campus, Shanghai, China
Yujie Shi
Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China
Jing Feng
Shanghai University of Medicine & Health Sciences Affiliated Sixth People’s Hospital South Campus, Shanghai, China; The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen), Shenzhen, China; School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangdong Province, Guangzhou, China
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; Academy of Biomedical Engineering, Kunming Medical University, Kunming, China; The Third Affiliated Hospital, Kunming Medical University, Kunming, China
Anti-tumor drug resistance is a challenge for human triple-negative breast cancer (TNBC) treatment. Our previous work demonstrated that TNFAIP2 activates RAC1 to promote TNBC cell proliferation and migration. However, the mechanism by which TNFAIP2 activates RAC1 is unknown. In this study, we found that TNFAIP2 interacts with IQGAP1 and Integrin β4. Integrin β4 activates RAC1 through TNFAIP2 and IQGAP1 and confers DNA damage-related drug resistance in TNBC. These results indicate that the Integrin β4/TNFAIP2/IQGAP1/RAC1 axis provides potential therapeutic targets to overcome DNA damage-related drug resistance in TNBC.
