CDKL1 facilitates tumorigenesis and metastasis of bladder urothelial carcinoma by activating SIRT1/Wnt/β-catenin signaling.

Abstract

Bladder urothelial carcinoma (BUC) is a common malignancy characterized by high recurrence and progression, and patients with advanced disease often have poor outcomes due to therapeutic resistance and limited targeted treatment options. In this study, we investigated the role of cyclin-dependent kinase-like 1 (CDKL1) in BUC progression. CDKL1 was markedly upregulated in BUC tissues, and elevated CDKL1 expression was significantly associated with unfavorable patient survival. Functional assays demonstrated that CDKL1 depletion suppressed BUC cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, CDKL1 interacted with sirtuin 1 (SIRT1), promoting SIRT1-mediated deacetylation of β-catenin, which activated β-catenin/TCF4 signaling. Activation of the β-catenin/TCF4 complex effectively rescued the inhibitory effects of CDKL1 knockdown on BUC cell proliferation and metastasis. These findings indicate that CDKL1 promotes BUC tumorigenesis and metastasis through activation of the Wnt/β-catenin/TCF4 signaling pathway via SIRT1-dependent β-catenin deacetylation, highlighting CDKL1 as a potential therapeutic target for BUC.