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Growth factor signaling pathways as targets for prevention of epithelial carcinogenesis

Authors

  • Okkyung Rho,

    1. Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
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    • Okkyung Rho and Dae Joon Kim contributed equally to this work.

  • Dae Joon Kim,

    1. Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
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    • Okkyung Rho and Dae Joon Kim contributed equally to this work.

  • Karou Kiguchi,

    1. Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
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  • John DiGiovanni

    Corresponding author
    1. Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas
    • University of Texas Dell Pediatric Research Institute, 1400, Barbara Jordan Boulevard, Room 2.228, Austin, TX 78723-3092.
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Abstract

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. © 2010 Wiley-Liss, Inc.

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