Emerging Roles of SKP2 in Cancer Drug Resistance

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 5; p. 1147
• Main Authors: Wu, Ting, Gu, Xinsheng, Cui, Hongmei
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 10-05-2021; MDPI
• Subjects: Akt; AKT protein; Apoptosis; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cell growth; Chemotherapy; Clinical trials; DNA damage; DNA repair; Drug resistance; Enzymes; Kinases; Localization; Lung cancer; Medical prognosis; Mesenchyme; Mitosis; Multiple myeloma; p27; Phosphorylation; Proteins; Review; Skp2; Transcription factors; Tumorigenesis; Tumors; Ubiquitin-protein ligase
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10051147

More than half of all cancer patients receive chemotherapy, however, some of them easily acquire drug resistance. Resistance to chemotherapy has become a massive obstacle to achieve high rates of pathological complete response during cancer therapy. S-phase kinase-associated protein 2 (Skp2), as an E3 ligase, was found to be highly correlated with drug resistance and poor prognosis. In this review, we summarize the mechanisms that Skp2 confers to drug resistance, including the Akt-Skp2 feedback loop, Skp2-p27 pathway, cell cycle and mitosis regulation, EMT (epithelial-mesenchymal transition) property, enhanced DNA damage response and repair, etc. We also addressed novel molecules that either inhibit Skp2 expression or target Skp2-centered interactions, which might have vast potential for application in clinics and benefit cancer patients in the future.