p53 signaling and autophagy in cancer: A revolutionary strategy could be developed for cancer treatment

Abstract

p53 as a tumor suppressor protein has been implicated in multiple aspects of biological processes, including apoptosis, cell cycle arrest, senescence, metabolism, differentiation and angiogenesis. Recently, several studies have shown that p53 can induce autophagy in both transcription-dependent and -independent manners. Nonetheless, p53 may also inhibit autophagy. In addition, p53 participates in homeostatic regulation of energy metabolism, oxidative stress and amino acid metabolism. Although the relationship between autophagy and p53 is quite complicated, and has not been well elucidated, p53 may underlie key aspects of metabolism and cancer biology. Thus, understanding the novel functions of p53 may allow us to develop new anticancer therapeutic approaches.

TP53-dependent autophagy links the ATR-CHEK1 axis activation to proinflammatory VEGFA production in human bronchial epithelial cells exposed to fine particulate matter (PM2.5)

“…33 The lysosomal protein DRAM1 is a transcriptional target of TP53 that can induce autophagosome accumulation and therefore orchestrates the induction of autophagy. 25 However, it is noteworthy that previous reports demonstrate the role of the TP53-DRAM1 pathway activation in modulating the autophagic process under genotoxic stress only, which is critical for cell-fate determination.…”

Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells

“…p53 promotes autophagy as a transcription factor in the nucleus by activating genes involved in apoptosis, cell cycle arrest and autophagy. However, autophagy is suppressed when cytosolic p53 expression is inhibited (15,51,52). In addition, p53 may induce autophagy by binding to the promoter region of multiple genes that code for pro-autophagic modulators, such as DRAM and TIGAR (53,54).…”

“…Both class I PI3K (PI3K-I)/Akt/ mammalian target of rapamycin (mTOR) and Beclin-1/class III PI3K (PI3K-III)/LC3-II signaling pathways are involved in pre-autophagosome formation (11)(12)(13)(14). Cytosolic and nuclear p53, damage-regulated autophagy modulator (DRAM) and the p53-induced glycolysis and apoptosis regulator (TIGAR) are involved in autophagosome formation (15). In addition, p53 initiates a cascade of starvation signals and triggers a starvation-like response by inhibiting mTOR (16).…”

“…In addition, p53 initiates a cascade of starvation signals and triggers a starvation-like response by inhibiting mTOR (16). Furthermore, p53 activates both the DRAM and PI3K-III pathways upon autophagosome formation (15). Phytochemicals or chemical agents that regulate p53-and PI3K-mediated autophagy induction could serve as a potential starting point for novel methods of cancer prevention and treatment.…”

“…Several genes involved in autophagy, such as the genes encoding Beclin-1, LC3-II and DRAM, are regulated by NF-κB (15,19,20). Regulation of NF-κB activation affects autophagy-relevant gene expression, leading to the induction of autophagy.…”