YKT6 Promotes Bladder Cancer Progression by Stabilizing β-catenin Through USP7-Mediated Deubiquitination

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Bladder cancer (BLCA) is a lethal malignancy with limited treatment options.
• Understanding the molecular drivers of BLCA is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of YKT6, a SNARE protein, in bladder cancer progression.
• To elucidate the molecular mechanisms by which YKT6 influences BLCA.
• To explore the therapeutic potential of targeting the YKT6 pathway.

Main Methods:

• Analysis of YKT6 expression in BLCA tissues and cell lines using public datasets and tissue microarrays.
• In vitro and in vivo functional assays to assess YKT6's impact on cell proliferation, migration, and metastasis.
• Investigating the interaction between YKT6, USP7, and beta-catenin using molecular and biochemical techniques.
• Pharmacological inhibition of Wnt signaling and genetic knockdown of USP7 to validate the pathway.

Main Results:

• YKT6 is significantly upregulated in BLCA and correlates with advanced tumor grade and poor prognosis.
• YKT6 promotes BLCA cell proliferation, migration, and metastasis.
• YKT6 activates the Wnt/beta-catenin pathway by recruiting USP7 to deubiquitinate and stabilize beta-catenin.
• Inhibition of Wnt signaling reverses YKT6-driven tumor progression, and USP7 knockdown abrogates YKT6's effects.

Conclusions:

• YKT6 acts as an oncogene in bladder cancer by regulating the YKT6/USP7/beta-catenin axis.
• This axis represents a novel therapeutic target for precision BLCA treatment.
• Targeting YKT6 offers a promising strategy for improving outcomes in bladder cancer patients.