TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly effect.
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.
Joshi
Amit
A
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.
Cao
Deliang
D
D000818:Animals; D018450:Disease Progression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology* / Q000378:metabolism
D053773:Transforming Growth Factor beta1