PKMYT1 induced by YAP/TEAD1 gives rise to the progression and worse prognosis of bladder cancer.

Abstract

Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), which is associated with progression of tumor, is upregulated in a variety of cancers. However, its expression and the underlying molecular mechanisms in the context of bladder cancer (BLCA) remain elusive. Here we found that PKMYT1 expression was markedly higher expression in BLCA, which was correlated with poorer prognosis compared with low expression. Knockdown of PKMYT1 significantly inhibited the BLCA cells proliferation in vivo and in vitro, and migration and invasion, reduced G2/M phase in cell cycle and induced apoptosis. Mechanically, YAP and TEAD1 knockdown suppressed PKMYT1 expression in BLCA cells, whereas overexpression of YAP upregulated PKMYT1 expression and YAP prompted PKMYT1 transcriptional expression via TEAD1-mediated direct binding to PKMYT1 promotor. Collectively, these findings suggest that PKMYT1, functioning as a direct gene target regulated by YAP/TEAD1, could serve as a potential indicator of progression and prognosis in BLCA. Further, PKMYT1 could serve as a novel therapeutic target for BLCA.