YAP/TAZ Pathway Promoted the Trastuzumab Resistance in HER2-Positive Breast Cancer

The developed resistance of trastuzumab remained a problem for clinical therapy of HER2-positive breast cancer. However, effects of YAP/TAZ pathway on resistance of trastuzumab have not been explored. Tumor tissues were collected from 40 breast cancer patients for clinical studies. For in vitro studies, human breast cancer cell lines SK-BR-3-TS was obtained, and trastuzumab resistant model SK-BR-3-TR was constructed. Cell viability was determined using MTT assay. Cell apoptosis was analyzed by flow cytometry. Protein and mRNA expression was measured using western blotting and RT-qPCR, respectively. The mRNA and protein level of YAP was significantly increased in the tumor tissues of HER2-positive breast cancer patients. Consistently, the expression of YAP and TAZ were both dramatically upregulated in SK-BR-3-TR cells. The cell viability was increased, while cell apoptosis was inhibited in SK-BR-3-TS cells compared with SK-BR-3-TS. The depletion of YAP by si-YAP reversed the YAP/TAZ expression, cell viability and cell apoptosis in SK-BR-3-TR cells. YAP/TAZ pathway might induce the trastuzumab resistance in HER2-positive breast cancer and targeting YAP would be an alternative way for the clinical therapeutic methods of HER2 positive breast cancer.