Cholesterol esterification and p53-mediated tumor suppression.
Cholesterol esterification and p53-mediated tumor suppression.
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DOI：
10.37349/etat.2023.00185
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Prochownik EV
中科院分区：
文献类型：
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作者：
Li Y;Karin M;Prochownik EV
许多人类癌症在肿瘤蛋白53（TP 53）肿瘤抑制基因中携带错义突变或缺失。TP 53的产物p53调节许多生物过程，包括细胞代谢。胆固醇是维持膜功能和组织稳态所需的关键脂质，同时也是类固醇激素和胆汁酸合成的前体。过量的胆固醇会导致其酯化和胆固醇酯的储存。最近的研究表明，p53的缺失导致胆固醇酯的过度生物合成，从而促进小鼠肝细胞癌。阻断胆固醇酯化可以改善治疗结果，特别是对于起源于非酒精性脂肪肝背景的p53缺失/突变的肝癌。
Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) tumor suppressor gene. TP53’s product, p53 regulates many biological processes, including cell metabolism. Cholesterol is a key lipid needed for the maintenance of membrane function and tissue homeostasis while also serving as a precursor for steroid hormone and bile acid synthesis. An over-abundance of cholesterol can lead to its esterification and storage as cholesterol esters. The recent study has shown that the loss of p53 leads to excessive cholesterol ester biosynthesis, which promotes hepatocellular carcinoma in mice. Blocking cholesterol esterification improves treatment outcomes, particularly for liver cancers with p53 deletions/mutations that originate in a background of non-alcoholic fatty liver disease.