TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key pr...TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.展开更多
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...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。展开更多
文摘TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.
文摘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。
