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Interplay between fatty acids, SCD, mTORC1 and YAP/TAZ in promoting hepatocellular carcinoma

  • Jihane N. Benhammou
    Affiliations
    Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095

    Greater Los Angeles Veterans Affairs Healthcare System, Gastroenterology, Hepatology and Parenteral Nutrition, Los Angeles, CA 90075
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  • Jim Sinnett-Smith
    Affiliations
    Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095
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  • Joseph R. Pisegna
    Affiliations
    Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095

    Greater Los Angeles Veterans Affairs Healthcare System, Gastroenterology, Hepatology and Parenteral Nutrition, Los Angeles, CA 90075
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  • Enrique J. Rozengurt
    Correspondence
    Corresponding author: Enrique J Rozengurt, DVM, PhD, AGAF, FRC Path (UK), CURE: Digestive Diseases Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
    Affiliations
    Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095

    Greater Los Angeles Veterans Affairs Healthcare System, Gastroenterology, Hepatology and Parenteral Nutrition, Los Angeles, CA 90075
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Open AccessPublished:August 02, 2022DOI:https://doi.org/10.1016/j.gastha.2022.07.017
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      Abstract

      Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions with one of its most consequential complications being hepatocellular carcinoma (HCC). NAFLD-related HCC is becoming the leading indication for liver transplantation in the USA. Given the scarcity of available organs, early detection and prevention remain key in prevention and management of the disease. Over the years, the YAP/TAZ pathway emerged as a key signal transduction pathway in the pathogenesis of HCC. In this review, we explore the interplay between the YAP/TAZ pathway as a point of convergence in HCC pathogenesis. We review the evidence of how lipid reprogramming and key lipid pathways, saturated and monounsaturated fatty acids (through the rate limiting enzyme stearoyl Co-A desaturase), the mevalonic acid pathway (the role of statins) and mTORC1 all play critical roles in intricate and complex network that tightly regulate the YAP/TAZ pro-oncogenic pathway.