Overexpression of enhancer of zeste homolog 2 ( EZH 2 ) and focal adhesion kinase ( FAK ) is associated with cancer metastasis and poor prognosis in breast cancer

Enhancer of zeste homolog 2 (EZH2), a polycomb histone methyltransferase, is a key epigenetic modifier implicated in the metastasis of various cancers. Focal adhesion kinase (FAK), a protein tyrosine kinase, modulates signaling and fundamental functions to facilitate cancer progression and metastasis. However, the link between EZH2 and FAK expression and their mechanisms in breast cancer (BC) remain ambiguous. In the present study, EZH2 and FAK expression was examined in two tissue microarrays containing specimens from 300 patients with breast cancer using immunohistochemistry. Kaplan-Meier survival analysis demonstrated that high expression of EZH2 (56.6%) and FAK (74.7%) was associated with poor prognosis (P < 0.05). In addition, univariate and multivariate Cox regression analyses suggest that FAK is an independent prognostic factor (ER status: hazard ratio (HR) = 0.776, 95% Confidence Interval (CI): 0.603-1.972; PR status: HR = 0.790, 95% CI: 0.338-1.061; AR status: HR = 0.934, 95% CI: 0.751-1.162; EZH2 status: HR = 1.376, 95% CI: 0.845-2.242; FAK status: HR = 2.117, 95% CI: 1.147-3.909, P = 0.016). In the nuclear grade II, negative Her2, negative EGFR status, or positive P53 status subgroups, patients expressing high EZH2 and FAK levels also presented with poor survival. Furthermore, invasion of MDA-MB-231 cells decreased after combined inhibition of EZH2 and FAK. Moreover, FAK protein levels were significantly downregulated in EZH2 knocked down cell lines in vitro. In conclusion, EZH2 and FAK expression is correlated and associated with BC prognosis.