title: Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis.
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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Hae-Yun
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Fattet
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.|Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D016326:Extracellular Matrix Proteins
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