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Comment
. 2021 Dec;10(6):910-912.
doi: 10.21037/hbsn-21-374.

STARD1: a new rising StAR in cholesterol-mediated hepatocarcinogenesis

Salvatore Papa  1 , Concetta Bubici  2 , Wing-Kin Syn  3   4   5
Affiliations
Comment

STARD1: a new rising StAR in cholesterol-mediated hepatocarcinogenesis

Salvatore Papa et al. Hepatobiliary Surg Nutr. 2021 Dec.
No abstract available

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/hbsn-21-374). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Simplified illustration of STARD1 regulation of cholesterol-driven NASH and HCC. Schematic illustration depicting how mitochondrial cholesterol contributes to the development of NASH-driven HCC. When the intracellular levels of cholesterol reach a certain threshold, it undergoes trafficking to different intracellular organelles, including mitochondria. STARD1 protein mediates cholesterol transport to the mitochondrial inner membrane, supplying cholesterol to CYP11A1 to generate pregnenolone in steroidogenic tissues, or to CYP27A1 to generate oxysterols (i.e., 27-OH cholesterol) in hepatocytes and other cells expressing this enzyme. Oxysterols are then metabolized into bile acids such as CDCA and CA, the two major primary bile acids synthesized in human livers that are conjugated with taurine or glycine for secretion into bile. The amount of bile acids accumulated in the liver are, therefore, strictly reliant on STARD1 expression levels that remain low in a normal functioning liver but increase several folds in response to acute liver injury and chronic liver disease, such as NASH—one of most prevalent causes of HCC. CDCA, chenodeoxycholic acid; CA, cholic acid; HCC, hepatocellular carcinoma; NASH, nonalcoholic steatohepatitis.
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Comment on

References

    1. Tabas I. Cholesterol in health and disease. J Clin Invest 2002;110:583-90. 10.1172/JCI0216381 - DOI - PMC - PubMed
    1. Giacomini I, Gianfanti F, Desbats MA, et al. Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy. Front Oncol 2021;11:682911. 10.3389/fonc.2021.682911 - DOI - PMC - PubMed
    1. Voisin M, de Medina P, Mallinger A, et al. Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor. Proc Natl Acad Sci U S A 2017;114:E9346-55. 10.1073/pnas.1707965114 - DOI - PMC - PubMed
    1. Liang JQ, Teoh N, Xu L, et al. Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling. Nat Commun 2018;9:4490. 10.1038/s41467-018-06931-6 - DOI - PMC - PubMed
    1. Conde de la Rosa L, Garcia-Ruiz C, Vallejo C, et al. STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway. J Hepatol 2021;74:1429-41. 10.1016/j.jhep.2021.01.028 - DOI - PMC - PubMed