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Role of TGF-β in Alcohol-Induced Liver Disease

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Alcohol and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1032))

Abstract

Over 90% of hepatocellular carcinoma (HCC) occurs against a background of chronic liver disease or cirrhosis induced from viral hepatitis to alcohol injury. One third of patients with cirrhosis will develop HCC during their lifetime, with a 3–5% annual incidence. However, little is known about the key mechanisms by which toxins mediate DNA damage in the liver. Recent studies support a central role for TGF-β signaling in conferring genomic stability yet the precise mechanism of action and the specific stages of tumor suppression remain unclear (Bornstein S, White R, Malkoski S, Oka M, Han G, Cleaver T, Reh D, Andersen P, Gross N, Olson S, Deng C, Lu SL, Wang XJ. J Clin Invest 119:3408–3419 (2009); Korc M. J Clin Invest 119:3208–3211 (2009); Glick A, Popescu N, Alexander V, Ueno H, Bottinger E, Yuspa SH. Proc Natl Acad Sci U S A 96:14949–14954 (1999)). Furthermore, it has recently been shown that β2SP+/− and β2SP+/−/Smad3+/− mice phenocopy a hereditary human cancer syndrome, the Beckwith-Wiedemann syndrome (BWS), which has an 800 fold risk of cancers including HCC, hepatoblastoma, and a range of liver disorders. Identifying key biological pathways and mechanisms for suppressing alcohol-induced stem cell injury and HCC will be critical for enhancing patient care and the employment of new therapeutic approaches.

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Authors and Affiliations

  1. Center for Translational Medicine, Department of Surgery and George Washington Cancer Center, George Washington University, Washington, DC, USA

    Wilma Jogunoori & Lopa Mishra

  2. Veterans Affairs Medical Center, Washington, DC, USA

    Wilma Jogunoori & Lopa Mishra

Authors
  1. Wilma Jogunoori
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  2. Lopa Mishra
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Correspondence to Lopa Mishra .

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Editors and Affiliations

  1. Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA

    Vasilis Vasiliou

  2. Distilled Spirits Council of the US, Washington, DC, USA

    Samir Zakhari

  3. Mishra Laboratory, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Lopa Mishra

  4. Salem Medical Centre, University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Helmut K. Seitz

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Jogunoori, W., Mishra, L. (2018). Role of TGF-β in Alcohol-Induced Liver Disease. In: Vasiliou, V., Zakhari, S., Mishra, L., Seitz, H. (eds) Alcohol and Cancer. Advances in Experimental Medicine and Biology, vol 1032. Springer, Cham. https://doi.org/10.1007/978-3-319-98788-0_7

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