Integrin β4 promotes DNA damage-related drug resistance in triple-negative breast cancer via TNFAIP2/IQGAP1/RAC1

Author:

Fang Huan12,Ren Wenlong13,Cui Qiuxia145ORCID,Liang Huichun1,Yang Chuanyu1,Liu Wenjing1,Wang Xinye1,Liu Xue6,Shi Yujie7,Feng Jing689,Chen Ceshi11011ORCID

Affiliation:

1. Kunming Institute of Zoology, Chinese Academy of Sciences

2. Kunming College of Life Sciences, University of Chinese Academy of Sciences

3. School of Life Science, University of Science & Technology of China

4. Affiliated Hospital of Guangdong Medical University

5. 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

6. Shanghai University of Medicine & Health Sciences Affiliated Sixth People’s Hospital South Campus

7. Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University

8. The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen)

9. School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangdong Province

10. Academy of Biomedical Engineering, Kunming Medical University

11. The Third Affiliated Hospital, Kunming Medical University

Abstract

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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

The Yunnan Fundamental Research Projects

The Guangdong Foundation Committee for Basic and Applied Basic Research projects

Yunnan (Kunming) Academician Expert Workstation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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