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Updated: Jan 12, 2026

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
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The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms

Ruicheng Wu1,2,3, Fanglin Shao4,5, Siang Boon Koh6

  • 1Urology & Nephrology Center, Department of Urology, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Cellular & Molecular Biology Letters
|November 5, 2025
PubMed

Insights

Interferon-stimulated gene 15 (ISG15) conjugation, or ISGylation, impacts cancer by influencing apoptosis, autophagy, immune evasion, metabolism, and stem cell maintenance. Understanding ISGylation

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Post-translational modifications regulate protein function and cellular signaling.
  • ISGylation, a ubiquitin-like modification, is mediated by ISG15.
  • ISGylation plays a critical role in cellular responses to interferon and viral infections.

Purpose of the Study:

  • To review the multifaceted roles of ISGylation in various tumor-associated phenotypes.
  • To elucidate the mechanisms by which ISGylation influences cancer progression.
  • To highlight the dual roles of ISGylation in processes like apoptosis and autophagy.

Main Methods:

  • Literature review of studies on ISGylation and cancer.
  • Analysis of ISGylation's impact on apoptosis, autophagy, immune escape, metabolism, cancer stem cells, and DNA damage repair.
  • Examination of ISG15 and ISGylation mechanisms in tumorigenesis.

Main Results:

  • ISGylation exhibits dual roles in apoptosis, promoting either survival or death.
  • It regulates autophagy, influencing tumor adaptation and immune responses.
  • ISGylation contributes to immune escape by affecting PD-L1 stability and immune cell infiltration.
  • It is involved in metabolic reprogramming, supporting tumor growth and therapeutic resistance.
  • ISGylation is crucial for maintaining cancer stem cell properties.
  • ISGylation impacts DNA damage repair mechanisms.

Conclusions:

  • ISGylation is a key regulator of diverse cancer-related processes.
  • Understanding ISGylation's mechanisms enhances insights into tumorigenesis and disease progression.
  • Targeting ISGylation pathways may offer novel therapeutic strategies for cancer.
Keywords:
Drug resistanceISGylationImmune evasionPost-translational modificationTumor microenvironment

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