TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect

Front Biosci (Landmark Ed). 2010 Jan 1;15:180-94. doi: 10.2741/3614.

Abstract

Transforming growth factor-beta (TGF-beta) signals through receptor serine/threonine kinases and intracellular Smad effectors, regulating numerous epithelial cell processes. TGF-beta plays a crucial role in the cancer initiation and progression through tumor cell autonomous signaling and interactions with tumor microenvironment, but is featured with a butterfly effect upon the stages of tumorigenesis. TGF-beta signaling acts as a suppressor of epithelial cell tumorigenesis at early stages, but promotes tumor progression by enhancing migration, invasion, and survival of the tumor cells during the later stages. TGF-beta signaling also cross-talks with other cell survival signaling pathways. Tumor microenvironment contains many distinct cell types, which substantially influences the tumor cell growth and survival, and the invasion and metastasis. TGF-beta in the microenvironment, produced by cancer and/or stromal cells, is high and negatively correlates with disease progression and patient prognosis. Therefore, TGF-beta may affect tumor progression by multiple mechanisms in addition to its direct action on tumor cells, and the diversities of TGF-beta signaling in tumors imply a need for caution to TGF-beta-targeted strategies of tumor prevention and/or therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Killer Cells, Natural / immunology
  • Models, Biological
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Signal Transduction / immunology*
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta1 / immunology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Transforming Growth Factor beta1