SKP2 E3 ligase in urological malignancies: a critical regulator of the cell cycle and therapeutic target

Abstract

SKP2, an E3 ubiquitin ligase component of the SCF complex, plays a critical role in cell cycle regulation by targeting key inhibitors like p27, p21, and p57 for degradation, thereby promoting G1-S transition. Its overexpression is strongly associated with urological malignancies, including prostate, bladder, and kidney cancers, where it correlates with aggressive disease and poor prognosis. SKP2 drives tumor progression, via enhancing cancer cell proliferation, invasion, and metastasis. Targeting SKP2 through small molecule inhibitors or combination therapies holds promise for cancer treatment. However, challenges remain, including understanding its role in cancer stem cells, metastasis, and treatment resistance. Continued research is essential to harness SKP2's potential as a therapeutic target and biomarker for personalized medicine in urological cancers.