Growth factor signaling pathways as targets for prevention of epithelial carcinogenesis.
Growth factor receptor (GFR) signaling controls epithelial cell growth by responding to various endogenous or exogenous stimuli and subsequently activating downstream signaling pathways including Stat3, PI3K/Akt/mTOR, MAPK, and c-Src. Environmental chemical toxicants and UVB irradiation cause enhanced and prolonged activation of GFR signaling and downstream pathways that contributes to epithelial cancer development including skin cancer. Recent studies, especially those with tissue-specific transgenic mouse models, have demonstrated that GFRs and their downstream signaling pathways contribute to all three stages of epithelial carcinogenesis by regulating a wide variety of biological functions including proliferation, apoptosis, angiogenesis, cell adhesion, and migration. Inhibiting these signaling pathways early in the carcinogenic process results in reduced cell proliferation and survival, leading to decreased tumor formation. Collectively, these studies suggest that GFR signaling and subsequent downstream signaling pathways are potential targets for the prevention of epithelial cancers including skin cancer.
Rho
Okkyung
O
Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78723-3092, USA.
Kim
Dae Joon
DJ
Kiguchi
Karou
K
Digiovanni
John
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D017978:Receptors, Growth Factor; D017526:Receptor, IGF Type 1