TTK promotes mitophagy by regulating ULK1 phosphorylation and pre-mRNA splicing to inhibit mitochondrial apoptosis in bladder cancer.

ABSTRACT: Bladder cancer (BC) remains a major global health challenge, with poor prognosis and limited therapeutic options in advanced stages. TTK protein kinase (TTK), a serine/threonine kinase, has been implicated in the progression of various cancers, but its role in BC has not been fully elucidated. In this study, we show that TTK is significantly upregulated in BC tissues and cell lines, correlating with poor patient prognosis. Functional assays revealed that TTK promotes proliferation and inhibits apoptosis of BC cells. Mechanistically, TTK enhances mitophagy by directly phosphorylating ULK1 at Ser477, thereby activating the ULK1/FUNDC1-mediated mitophagy pathway. TTK knockdown disrupts mitophagy, leading to impaired clearance of damaged mitochondria, excessive accumulation of mitochondrial re

SUBMITTER: Chen K 

PROVIDER: S-EPMC12432130 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature