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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 6/2008

Open Access 01-10-2008 | Original Article

Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions

Authors: Sharon Barr, Stuart Thomson, Elizabeth Buck, Suzanne Russo, Filippo Petti, Izabela Sujka-Kwok, Alexandra Eyzaguirre, Maryland Rosenfeld-Franklin, Neil W. Gibson, Mark Miglarese, David Epstein, Kenneth K. Iwata, John D. Haley

Published in: Clinical & Experimental Metastasis | Issue 6/2008

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Abstract

Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis.
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Metadata
Title
Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions
Authors
Sharon Barr
Stuart Thomson
Elizabeth Buck
Suzanne Russo
Filippo Petti
Izabela Sujka-Kwok
Alexandra Eyzaguirre
Maryland Rosenfeld-Franklin
Neil W. Gibson
Mark Miglarese
David Epstein
Kenneth K. Iwata
John D. Haley
Publication date
01-10-2008
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6/2008
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-007-9121-7

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