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Role of TGF-β in Alcohol-Induced Liver Disease

  • Wilma Jogunoori
  • Lopa MishraEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Hepatocellular Carcinoma Cirrhosis TGF-β Beckwith-Wiedemann syndrome 

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Center for Translational Medicine, Department of Surgery and George Washington Cancer CenterGeorge Washington UniversityWashington, DCUSA
  2. 2.Veterans Affairs Medical CenterWashington, DCUSA

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