Correlation between Notch signaling pathway and YAP1/TAZ in breast cancer / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the relationship of Notch1 expression with YAP1/TAZ expression in breast cancer and its possible mechanism. Methods: MDA-MB-231 and MCF-7 breast cancer cells were selected, and lentiviruses were used to construct stable infected cell lines with different expression levels of Notch1 and YAP1. Western blotting, RT-qPCR and co-immunoprecipitation were used to study the relationship between Notch1 and YAP1/TAZ expressions. Results: On the gene expression profiling interactive analysis (GEPIA) website, we analyzed the breast cancer data in the Cancer Gene Atlas Database (TCGA) and found that the expressions of Notch1 and YAP1/TAZ were positively correlated. Compared with those in the control group, the protein and mRNA levels of YAP1/TAZ in the shNotch1 group were reduced (P0.05). Co-immunoprecipitation showed that TAZ protein interacted with Notch1 and β-TrCP protein. Compared with those in the control group, the mRNA and protein levels of Notch1 and JAG1 in shYAP1 group were reduced (P<0.05), while those in YAP1 group were increased (P<0.05). TEAD family was predicted to be a JAG1 transcription factor on the JASPAR 2018 website. TEAD1/3/4 siRNA could effectively inhibit TEAD1/3/4 expression, and JAG1 expression decreased too (P<0.05). Conclusion: There is a positive feedback loop between Notch1 and YAP1/TAZ in breast cancer. YAP1/TAZ-TEAD can activate the Notch1 signaling pathway by regulating JAG1 expression. Notch1 protein can affect the degradation of YAP1/TAZ protein.