Roles of Mutant TP53 Gene in Cancer Development and Progression

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.