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PIAS family in cancer: from basic mechanisms to clinical applications

Xiaomeng Li1, Azhar Rasul2, Farzana Sharif2

  • 1KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.

Frontiers in Oncology
|April 9, 2024
PubMed

Insights

Protein inhibitors of activated STATs (PIAS) regulate gene transcription and are implicated in cancer. Targeting PIAS proteins and their SUMOylation pathways offers a potential therapeutic strategy for inhibiting cancer growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Signal Transduction

Background:

  • Protein inhibitors of activated STATs (PIAS) are key regulators of cytokine signaling and gene transcription.
  • PIAS proteins modulate approximately 60 other proteins, acting as versatile cellular regulators.
  • Dysregulation of PIAS is linked to aberrant gene expression driving oncogenic signaling in various cancers, with PIAS1 and PIAS3 frequently implicated.

Purpose of the Study:

  • To review the role of PIAS and SUMOylation in modulating transcriptional factor control.
  • To provide an update on the antagonistic functions of PIAS in different cancer types.
  • To highlight PIAS proteins as therapeutic targets for inhibiting the STAT pathway in cancers.

Main Methods:

  • Literature review synthesizing evidence on PIAS function in cancer.
  • Analysis of PIAS and SUMOylation mechanisms in transcriptional regulation.
  • Focus on PIAS1 and PIAS3 roles in cancer development and progression.

Main Results:

  • PIAS proteins, acting as SUMO E3 ligase factors, promote SUMOylation of transcription factors crucial for cancer cell survival, proliferation, and differentiation.
  • Impaired PIAS-mediated SUMOylation contributes to tumorigenesis.
  • Modulated expression of PIAS family members is observed in cancer cells.

Conclusions:

  • PIAS proteins are critical regulators of STAT signaling and play a significant role in cancer.
  • Targeting PIAS proteins represents a promising therapeutic strategy to inhibit STAT pathways in cancer.
  • Natural activators of PIAS pathways may hold potential for cancer treatment.
Keywords:
PIASSUMOylationactivators of transcription factor (STAT)signal transducerstranscriptional factor

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