SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• The ubiquitin-proteasome system (UPS) regulates protein homeostasis and is implicated in disease.
• S-phase kinase-associated protein 2 (SKP2), an E3 ubiquitin ligase in the UPS, targets proteins for degradation or functional modulation.
• SKP2 overexpression correlates with poor prognosis in multiple cancers, highlighting its oncogenic significance.

Purpose of the Study:

• To review the oncogenic properties and mechanisms of SKP2 across various cancer types.
• To explore the expanded roles of SKP2 beyond cell cycle control.
• To summarize future strategies for SKP2-targeted cancer therapy.

Main Methods:

• Literature review of studies on SKP2 function in cancer.
• Analysis of SKP2's role in protein degradation via ubiquitination.
• Examination of SKP2's involvement in metabolism, DNA repair, stemness, TME, and immunotherapy.

Main Results:

• SKP2 overexpression is a common feature in many cancers, linked to adverse clinical outcomes.
• SKP2's functions extend to critical cancer hallmarks including metabolism, DNA repair, stemness, and the tumor microenvironment.
• SKP2 influences response to immunotherapy, suggesting broader therapeutic implications.

Conclusions:

• SKP2 is a versatile oncogene with multifaceted roles in cancer development and progression.
• Targeting SKP2 presents a promising therapeutic avenue for a wide range of cancers.
• Further research into SKP2-targeted therapies is warranted to improve patient outcomes.