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Clin Cancer Res. 2015 Mar 1;21(5):962-968. doi: 10.1158/1078-0432.CCR-13-3173. Epub 2014 Aug 8.

Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis.

Author information

1
Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
2
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
#
Contributed equally

Abstract

During tumor development, tumor cells constantly communicate with the surrounding microenvironment through both biochemical and biophysical cues. In particular, the tumor microenvironment can instruct carcinoma cells to undergo a morphogenesis program termed epithelial-to-mesenchymal transition (EMT) to facilitate local invasion and metastatic dissemination. Growing evidence uncovered a plethora of microenvironmental factors in promoting EMT, including proinflammatory cytokines secreted by locally activated stromal cells, hypoxia conditions, extracellular matrix components, and mechanical properties. Here, we review various biochemical and biophysical factors in the tumor microenvironment that directly impinge upon the EMT program. Specifically, cytokines such as TGFβ, TNFα, and IL6 and hypoxia are capable of inducing EMT in various tumors. Several extracellular matrix (ECM) proteins, including collagen-I, fibronectin, and hyaluronan, and ECM remodeling via extracellular lysyl oxidase are also implicated in regulating EMT. In preclinical studies and ongoing clinical trials, targeting these tumor microenvironmental signals has shown promises in halting tumor progression in various human cancers.

PMID:
25107915
PMCID:
PMC4320988
DOI:
10.1158/1078-0432.CCR-13-3173
[Indexed for MEDLINE]
Free PMC Article

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