Journal
ANNALS OF ONCOLOGY
Volume 18, Issue 10, Pages 1605-1619Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdm070
Keywords
cancer progenitor cells; epithelial-mesenchymal transition; invasion; metastasis; stromal microenvironment; targeting therapies
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Funding
- NCI NIH HHS [CA78590, CA111294] Funding Source: Medline
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In this review, we describe the critical functions assumed by the interplay of epidermal growth factor, hedgehog, Wnt/beta-catenin, tumor growth factor-P and integrir signaling cascades in tumorigenic and migrating cancer progenitor cells and activated stromal cells during carcinogenesis. These growth factors provide an important role for the sustained growth and survival of tumorigenic cancer progenitor cells and their progeny by up-regulating numerous mitotic and antiapoptotic signaling cascades. Furthermore, these potent morphogens may cooperate for inducing the molecular events associated with the epithelial-mesenchymal program in cancer cells including the alterations in epithelial cell shape and motility through the dissociation of intercellular adherens junctions. Of therapeutic interest, new strategies for the development of more effective clinical treatments against the locally aggressive and invasive cancers based on the molecular targeting of deregulated signaling elements in tumorigenic and migrating cancer cells and their local microenvironment are also described.
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