Annals of Oncology Advance Access originally published online on March 12, 2007
Annals of Oncology 2007 18(10):1605-1619; doi:10.1093/annonc/mdm070
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© 2007 European Society for Medical Oncology
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Interplay of distinct growth factors during epithelial–mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies
Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, USA
Correspondence to: Dr M. Mimeault and Prof S. K. Batra, Department of Biochemistry and Molecular Biology, Department of Pathology and Microbiology, Eppley Institute of Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA. Tel: +1-402-559-5455; Fax: +1-402-559-6650; E-mail: mmimeault{at}unmc.edu and sbatra{at}unmc.edu
In this review, we describe the critical functions assumed by the interplay of epidermal growth factor, hedgehog, Wnt/ß-catenin, tumor growth factor-ß and integrin 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.
Key words: cancer progenitor cells, epithelial–mesenchymal transition, invasion, metastasis, stromal microenvironment, targeting therapies
Received for publication December 4, 2006. Revision received January 28, 2007. Accepted for publication January 30, 2007.
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