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Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal
transition in metastasis
#MMPMID25107915
Jung HY
; Fattet L
; Yang J
Clin Cancer Res
2015[Mar]; 21
(5
): 962-968
PMID25107915
show ga
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 TGF?,
TNF?, 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.
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