Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma
Authors
Bates, Richard C.Bellovin, David I.
Brown, Courtney
Maynard, Elizabeth
Wu, Bingyan
Kawakatsu, Hisaaki
Sheppard, Dean
Oettgen, Peter
Mercurio, Arthur M.
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2005-01-26Keywords
AnimalsAutocrine Communication
Carcinoma
Colonic Neoplasms
Female
Gene Expression Regulation, Neoplastic
Humans
Integrin alpha5
Integrin beta Chains
Intestinal Mucosa
Mesoderm
Mice
Mice, Nude
Neoplasm Invasiveness
Prognosis
Transcription, Genetic
Transforming Growth Factor beta
Tumor Markers, Biological
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
We used a spheroid model of colon carcinoma to analyze integrin dynamics as a function of the epithelial-mesenchymal transition (EMT), a process that provides a paradigm for understanding how carcinoma cells acquire a more aggressive phenotype. This EMT involves transcriptional activation of the beta6 integrin subunit and a consequent induction of alphavbeta6 expression. This integrin enhances the tumorigenic properties of colon carcinoma, including activation of autocrine TGF-beta and migration on interstitial fibronectin. Importantly, this study validates the clinical relevance of the EMT. Kaplan-Meier analysis of beta6 expression in 488 colorectal carcinomas revealed a striking reduction in median survival time of patients with high beta6 expression. Elevated receptor expression did not simply reflect increasing tumor stage, since log-rank analysis showed a more significant impact on the survival of patients with early-stage, as opposed to late-stage, disease. Cox regression analysis confirmed that this integrin is an independent variable for these tumors. These findings define the alphavbeta6 integrin as an important risk factor for early-stage disease and a novel therapeutic candidate for colorectal cancer.Source
J Clin Invest. 2005 Feb;115(2):339-47. Link to article on publisher's siteDOI
10.1172/JCI23183Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26265PubMed ID
15668738Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI23183