突变型p53与甲羟戊酸途径之间的调控机制

Regulatory Mechanism between Mutant p53 and Mevalonate Pathway

在肿瘤的发生发展过程中通常伴随肿瘤细胞代谢的重编程,以满足其对肿瘤微环境的适应及能量的获取。脂质代谢异常目前已成为肿瘤细胞代谢重编程的主要标志之一,而甲羟戊酸途径(mevalonate pathway,MVA)作为脂质代谢中重要的胆固醇生物合成途径,在肿瘤细胞中呈异常活跃状态。肿瘤细胞中突变型p53(mutant p53,mutp53)的代谢重组功能与MVA途径的活跃状态有密不可分的关系,mutp53可通过固醇类转录因子SREBP2(sterol response element binding protein 2)激活MVA途径,并进一步稳定自身表达,两者之间的相互作用促进了肿瘤细胞的异常增殖。该文通过对肿瘤细胞中mutp53与MVA途径之间相互调控机制的最新研究进展进行综述,为探寻靶向mutp53和MVA途径的新的肿瘤治疗方案提供思路。

The development of tumors is usually accompanied by the reprogramming of tumor cell metabolism to meet its adaptation to the tumor microenvironment and energy acquisition.Abnormal lipid metabolism has become one of the signs of metabolic changes in tumors.The MVA (mevalonate pathway),as an important cholesterol biosynthetic pathway in lipid metabolism,is active in tumor cells.The metabolic recombination function of mutp53 (mutant p53) in tumor cells is closely related to the active state of the MVA pathway.mutp53 can abnormally activate the MVA pathway through the sterol transcription factor SREBP2 (sterol response element binding protein 2) and further stabilize its own expression,and their interaction promotes the abnormal proliferation of tumor cells.This paper reviews the latest research progresses of the mutual regulation mechanism between mutp53 and MVA pathway,and provides new ideas for the cancer therapy targeting mutp53 and MVA pathway.