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Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton

Jihane N. Benhammou, Bo Qiao, Arthur Ko, James Sinnett‐Smith, Joseph R. Pisegna, Enrique Rozengurt

2023American Journal of Physiology-Gastrointestinal and Liver Physiology11 citationsDOIOpen Access PDF

Abstract

Statins are widely used for the treatment of cardiovascular diseases. Recently, their use has been associated with a decrease in the incidence of hepatocellular carcinoma (HCC); however, their mechanism(s) has remained elusive. In this study, we delineate the mechanism by which statins affect the Yes-associated protein (YAP), which has emerged as a key oncogenic pathway in HCC. We investigate each step of the mevalonate pathway and demonstrate that statins regulate YAP via Rho GTPases.

Topics & Concepts

CoactivatorActin cytoskeletonCytoskeletonCell biologyActinChemistryCancer researchBiologyCellTranscription factorBiochemistryGeneHippo pathway signaling and YAP/TAZLipid metabolism and biosynthesisProtein Kinase Regulation and GTPase Signaling
Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton | Litcius