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Transforming growth factor-beta in cancer and metastasis

Sonia B Jakowlew1

  • 1National Cancer Institute, Cell and Cancer Biology Branch, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA. jakowles@mail.nih.gov

Cancer Metastasis Reviews
|September 5, 2006
PubMed

Insights

Transforming growth factor-beta (TGF-beta) has a dual role in cancer, acting as a tumor suppressor early on and a tumor promoter in later stages. Understanding TGF-beta signaling is key for cancer treatment and prevention.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-beta) is a key cytokine regulating numerous cellular functions, including proliferation and apoptosis.
  • Its actions are context-dependent, influenced by cell type, environment, and other growth factors.
  • TGF-beta exhibits a dual role in tumorigenesis, acting as both a tumor suppressor and a pro-oncogenic factor.

Purpose of the Study:

  • To elucidate the complex and often contradictory roles of TGF-beta in cancer development and progression.
  • To explore the implications of TGF-beta signaling pathway alterations in human cancers.
  • To assess the potential of TGF-beta pathway components as biomarkers and therapeutic targets.

Main Methods:

  • Review and synthesis of existing literature on TGF-beta function in cellular processes and cancer.
  • Analysis of TGF-beta's impact on cell proliferation, differentiation, migration, apoptosis, angiogenesis, and immune surveillance.
  • Examination of alterations in TGF-beta signaling and cell cycle pathways in various human cancers.

Main Results:

  • TGF-beta inhibits normal epithelial cell proliferation, suggesting a tumor suppressor function.
  • Loss of TGF-beta responsiveness can promote malignant progression, indicating a pro-oncogenic role.
  • In later cancer stages, TGF-beta can promote invasion, angiogenesis, metastasis, and inhibit immune surveillance.
  • Resistance to TGF-beta is common in human cancers, linked to pathway alterations.

Conclusions:

  • TGF-beta acts as a tumor suppressor in early tumorigenesis by inhibiting proliferation and inducing apoptosis.
  • In advanced cancers, TGF-beta can promote tumor growth, invasion, metastasis, and angiogenesis.
  • TGF-beta signaling pathway members are promising predictive biomarkers and therapeutic targets for cancer and metastasis.

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