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The multifaceted roles of ISG15 in cancer: Conjugated and free forms

Xinran Liu1, Qiujin Ma2, Zhao Jia2

  • 1Tongji School of Pharmacy, Huazhong University of Science & Technology, Wuhan 430030, China; Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|October 11, 2025
PubMed

Insights

Interferon-stimulated gene product 15 (ISG15) plays dual roles in cancer, acting as a conjugated or free protein. Understanding ISG15

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Interferon-stimulated gene product 15 (ISG15) is a ubiquitin-like modifier.
  • ISG15 exerts functions through both conjugated (ISGylation) and free forms.
  • ISG15 has emerged as a critical factor in cancer progression.

Purpose of the Study:

  • To summarize the oncogenic characteristics associated with ISG15.
  • To review ISG15-regulated oncogenic pathways and molecular mechanisms.
  • To explore potential cancer interventions targeting ISG15.

Main Methods:

  • Literature review of ISG15's roles in cancer.
  • Analysis of ISG15's involvement in cancer stemness, invasion, metastasis, anti-apoptosis, and drug resistance.
  • Examination of ISG15-regulated oncogenic pathways.

Main Results:

  • ISG15 contributes to cancer stemness, invasion, metastasis, anti-apoptosis, and drug resistance.
  • ISG15 regulates diverse oncogenic pathways through its distinct forms.
  • Molecular regulations of ISG15 vary across different cancer types.

Conclusions:

  • ISG15 significantly impacts tumor pathogenesis through its multifaceted roles.
  • Targeting ISG15 presents a potential strategy for cancer therapy.
  • Further research into ISG15's molecular mechanisms can inform novel therapeutic approaches.
Keywords:
Cancer therapyISG15ISGylationImmune modulationUbiquitin-like protein

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