| First Author | Shen ZQ | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 8 | Pages | 2198-2211 |
| PubMed ID | 29166610 | Mgi Jnum | J:255236 |
| Mgi Id | MGI:6104063 | Doi | 10.1016/j.celrep.2017.10.099 |
| Citation | Shen ZQ, et al. (2017) CISD2 Haploinsufficiency Disrupts Calcium Homeostasis, Causes Nonalcoholic Fatty Liver Disease, and Promotes Hepatocellular Carcinoma. Cell Rep 21(8):2198-2211 |
| abstractText | CISD2 is located within the chromosome 4q region frequently deleted in hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a phenotype similar to the clinical manifestation of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cisd2 haploinsufficiency causes a low incidence (20%) of spontaneous HCC and promotes HBV-associated and DEN-induced HCC; conversely, 2-fold overexpression of Cisd2 suppresses HCC in these models. Mechanistically, Cisd2 interacts with Serca2b and mediates its Ca(2+) pump activity via modulation of Serca2b oxidative modification, which regulates ER Ca(2+) uptake and maintains intracellular Ca(2+) homeostasis in the hepatocyte. CISD2 haploinsufficiency disrupts calcium homeostasis, causing ER stress and subsequent NAFLD and NASH. Hemizygous deletion and decreased expression of CISD2 are detectable in a substantial fraction of human HCC specimens. These findings substantiate CISD2 as a haploinsufficient tumor suppressor and highlights Cisd2 as a drug target when developing therapies to treat NAFLD/NASH and prevent HCC. |
