Current insights into the regulation of programmed cell death by TP53 mutation in cancer

Abstract

Gene mutation is a complicated process that influences the onset and progression of cancer, and the most prevalent mutation involves the TP53 gene. One of the ways in which the body maintains homeostasis is programmed cell death, which includes apoptosis, autophagic cell death, pyroptosis, ferroptosis, NETosis, and the more recently identified process of cuprotosis. Evasion of these cell deaths is a hallmark of cancer cells, and our elucidation of the way these cells die helps us better understands the mechanisms by which cancer arises and provides us with more ways to treat it.Studies have shown that programmed cell death requires wild-type p53 protein and that mutations of TP53 can affect these modes of programmed cell death. For example, mutant p53 promotes iron-dependent cell death in ferroptosis and inhibits apoptotic and autophagic cell death. It is clear that TP53 mutations act on more than one pathway to death, and these pathways to death do not operate in isolation. They interact with each other and together determine cell death. This review focuses on the mechanisms via which TP53 mutation affects programmed cell death. Clinical investigations of TP53 mutation and the potential for targeted pharmacological agents that can be used to treat cancer are discussed.

The regulatory effects of p53 on the typical and atypical ferroptosis in the pathogenesis of osteosarcoma: A systematic review

“…Different studies have shown that atypical ferroptosis is either increased or decreased in osteosarcoma. Six studies ( Bouchalova et al, 2014 ; Xie et al, 2016 ; Gnanapradeepan et al, 2018 ; Su et al, 2022 ; Babamohamadi et al, 2022 ) have reported that atypical ferroptosis is enhanced in osteosarcoma. Table 4 summarizes the regulatory mechanisms of p53 on atypical ferroptosis.…”

“…Comparing the outcomes reported in Table 4 and the pathway illustrated in Figure 7 , we could deduce two possibilities from the regulatory outcomes of p53: enhanced ferroptosis or inhibited ferroptosis ( de Azevedo et al, 2019 ). Several studies ( Bouchalova et al, 2014 ; Xie et al, 2016 ; Gnanapradeepan et al, 2018 ; Su et al, 2022 ; Babamohamadi et al, 2022 ) have indicated that upregulation of p53 enhances atypical ferroptosis in the course of osteosarcoma, whereas other studies ( Komori, 2016 ; Van Maerken et al, 2014 ; Pang et al, 2020 ; Saraf et al, 2018 ; Yang and Zhang, 2013 ; Leroy et al, 2017 ) have reported that inactivation of p53 downregulates atypical ferroptosis in osteosarcoma.…”

“…We found evidence opposing the outcomes of p53 inactivation in ferroptosis in the course of osteosarcoma. Several studies (Bouchalova et al, 2014;Xie et al, 2016;Gnanapradeepan et al, 2018; Frontiers in Genetics frontiersin.org Babamohamadi et al, 2022;Su et al, 2022) have contended that p53 plays a central role in up-regulating atypical ferroptosis in the course of osteosarcoma through increasing the production of ROS, lipid and iron-mediated cell death, and cell proliferation (Table 4) (Liu and Gu, 2022b). Upregulation of atypical ferroptosis unfolds through increased production of ROS, lipid peroxidation and enhanced cell proliferation.…”

Silencing of FAM111B inhibits tumor growth and promotes apoptosis by decreasing AKT activity in ovarian cancer

“…Furthermore, p53 was reported to promote caspase-1 expression and enhance the expression of IL-1β and IL-18, to induce pyroptosis. 31 Upregulation of p53 in the FAM111B knockdown group may lead to increased levels of caspase-1, followed by IL-1β and IL-18. However, further studies are warranted to determine whether pyroptosis is related to the function of FAM111B in ovarian cancer.…”

A testis-specific lncRNA functions as a post-transcriptional regulator of MDM2 and stimulates apoptosis of testicular germ cell tumor cells

“…MDM2 is a major negative regulator of p53, promoting ubiquitindependent proteasomal degradation of p53 as an E3 ubiquitin ligase and repressing p53 transcriptional activation [4,5]. The tumor suppressor p53 is commonly mutated in various types of cancers [6,7], whereas it is often overexpressed and rarely mutated in TGCTs [3]. Accordingly, MDM2 overexpression in TGCTs is predicted to affect the activity of wild-type p53; however, the molecular mechanisms underlying the sensitivity or resistance of TGCTs to chemotherapy remain unclear.…”