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Tumor suppressor genes in the tumor microenvironment

Bahareh Tabanifar1, Hannah Lau2,3, Kanaga Sabapathy3

  • 1Division of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore 168583.

Disease Models & Mechanisms
|March 20, 2025
PubMed

Insights

Tumor suppressor genes (TSGs) regulate tumor growth not only within cancer cells but also in the tumor microenvironment (TME). Understanding TSG roles in the TME is crucial for developing effective cancer therapies.

Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Tumor suppressor genes (TSGs) traditionally viewed as acting autonomously within cancer cells.
  • The tumor microenvironment (TME) significantly impacts cancer development and progression.
  • Emerging evidence suggests TSGs function within TME cells to influence tumorigenesis.

Purpose of the Study:

  • To explore the role of TSGs in non-cancerous cells within the TME.
  • To examine the impact of TSG expression and deletion in the TME on tumor development.
  • To propose models for TSG function in the TME and discuss therapeutic implications.

Main Methods:

  • Analysis of TSG expression in clinical samples.
  • Utilizing mouse models with selective TSG deletion in the TME.
  • Case studies using TP53 and PTEN as exemplary TSGs.

Main Results:

  • Expression analyses and TME-specific TSG deletion studies indicate a functional role for TSGs in tumor development.
  • TP53 and PTEN demonstrate significant roles in TME cells for regulating tumor progression.
  • Postulation of 'pro-active' and 'reactive' models for TSG contributions to tumor growth based on event timing.

Conclusions:

  • TSGs play a critical role in regulating tumor development through their action within the TME.
  • The temporal dynamics of initiating events influence whether TSG roles are 'pro-active' or 'reactive'.
  • A combined therapeutic strategy targeting both cancer cells and the TME is necessary for improved cancer clearance.
Keywords:
FibroblastsPTENTP53Tumor microenvironmentTumor suppressors

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