Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies.
In this review, we describe the critical functions assumed by the interplay of epidermal growth factor, hedgehog, Wnt/beta-catenin, tumor growth factor-beta 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.
Mimeault
M
M
Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA. mmimeault@unmc.edu
Batra
S K
SK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology*; D066246:ErbB Receptors / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D008648:Mesoderm / Q000473:pathology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000502:physiology
D016207:Cytokines; D006133:Growth Substances; D053823:Hedgehog Proteins; D016023:Integrins; D051176:beta Catenin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors