Abstract Anti-tumor drug resistance is a challenge for human triple-negative breast cancer treatment. Our previous work demonstrated that TNFAIP2 activates RAC1 to promote triple-negative breast cancer 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 triple-negative breast cancer. These results indicate that the Integrin β4/TNFAIP2/IQGAP1/RAC1 axis provides potential therapeutic targets to overcome DNA damage-related drug resistance in triple-negative breast cancer.

Integrin beta4 promotes DNA damage drug resistance in triple-negative breast cancer via TNFAIP2/IQGAP1/Rac1