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

doi:10.7554/eLife.88483

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

Elife. 2023 Oct 3:12:RP88483. doi: 10.7554/eLife.88483.

Authors

Huan Fang^#^{1

2}, Wenlong Ren^#^{1

3}, Qiuxia Cui^#^{1

4

5}, Huichun Liang^#¹, Chuanyu Yang¹, Wenjing Liu¹, Xinye Wang¹, Xue Liu⁶, Yujie Shi⁷, Jing Feng^{6

8

9}, Ceshi Chen^{1

10

11}

Affiliations

¹ Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
² Kunming College of Life Sciences, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
³ School of Life Science, University of Science & Technology of China, Hefei, China.
⁴ Affiliated Hospital of Guangdong Medical University, Guangdong, China.
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, Shenzhen, China.
⁶ Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai, China.
⁷ Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China.
⁸ The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen), Shenzhen, China.
⁹ School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangdong Province, Guangzhou, China.
¹⁰ Academy of Biomedical Engineering, Kunming Medical University, Kunming, China.
¹¹ The Third Affiliated Hospital, Kunming Medical University, Kunming, China.

^# Contributed equally.

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.

Keywords: IQGAP1; ITGB4; RAC1; TNFAIP2; cancer biology; drug resistance; human; triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cytokines
Drug Resistance
Humans
Integrin beta4 / genetics
Integrin beta4 / metabolism
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / genetics
Triple Negative Breast Neoplasms* / pathology
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism

Substances

IQ motif containing GTPase activating protein 1
Integrin beta4
rac1 GTP-Binding Protein
TNFAIP2 protein, human
Cytokines
RAC1 protein, human

Grants and funding

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.