IMR Press / FBL / Volume 15 / Issue 1 / DOI: 10.2741/3614

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

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

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1 Department of Medical Microbiology, Immunology, and Cell Biology, SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine. 913 N. Rutledge Street, Springfield, IL 62702, USA
Academic Editor:Kounosuke Watabe
Front. Biosci. (Landmark Ed) 2010, 15(1), 180–194; https://doi.org/10.2741/3614
Published: 1 January 2010
(This article belongs to the Special Issue Pathogenesis of tumor progression in breast and prostate cancer)
Abstract

Transforming growth factor-beta (TGF-β) signals through receptor serine/threonine kinases and intracellular Smad effectors, regulating numerous epithelial cell processes. TGF-β 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-β 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-β 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-β in the microenvironment, produced by cancer and/or stromal cells, is high and negatively correlates with disease progression and patient prognosis. Therefore, TGF-β may affect tumor progression by multiple mechanisms in addition to its direct action on tumor cells, and the diversities of TGF-β signaling in tumors imply a need for caution to TGF-β-targeted strategies of tumor prevention and/or therapeutics.

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