ZEB1 stimulates breast cancer growth by up-regulating hTERT expression

Highlights: • hTERT expression is positively correlated with ZEB1 expression in breast cancer. • ZEB1 promotes hTERT expression and telomerase activity in breast cancer cell lines. • ZEB1 increases the transcriptional activity of the hTERT promoter but does not bind to the E-box. • ZEB1 controls hTERT expression by interacting with the co-activator Yes-associated protein (YAP). Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced. Finally, we verified that ZEB1, which mostly functions as a transcriptional repressor, can recruit the co-activator YAP to enhance the transcriptional activation of hTERT. Fascinatingly, instead of acting on E-boxes, the ZEB1/YAP complex tends to function as a transcriptional activator by binding with sequences potentially located in the hTERT promoter. Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.