p53: Protection against Tumor Growth beyond Effects on Cell Cycle and Apoptosis

Abstract

The tumor suppressor p53 has established functions in cancer. Specifically, it has been shown to cause cell-cycle arrest and apoptosis in response to DNA damage. It is also one of the most commonly mutated or silenced genes in cancer and for this reason has been extensively studied. Recently, the role of p53 has been shown to go beyond its effects on cell cycle and apoptosis, with effects on metabolism emerging as a key contributor to cancer growth in situations where p53 is lost. Beyond this, the role of p53 in the tumor microenvironment is poorly understood. The publication by Wang and colleagues demonstrates for the first time that p53 is a key negative regulator of aromatase and, hence, estrogen production in the breast tumor microenvironment. It goes further by demonstrating that an important regulator of aromatase, the obesity-associated and tumor-derived factor prostaglandin E 2 , inhibits p53 in the breast adipose stroma. This review presents these findings in the context of established and emerging roles of p53 and discusses possible implications for the treatment of breast cancer. Cancer Res; 75(23); 5001-7. Ó2015 AACR.

Activated p53 with Histone Deacetylase Inhibitor Enhances L-Fucose-Mediated Drug Delivery through Induction of Fucosyltransferase 8 Expression in Hepatocellular Carcinoma Cells

“…[16,17] Beside its tumor suppressor function, p53 acts as a transcription factor to regulate a number of signaling pathways. [18] However, to date, the relationship between FUT8 and p53 has not been investigated.…”

Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells

“…However, in response to stress, p53 is stabilized and activated by PTMs that inhibit its interaction with MDM-2 and promote interactions with co-factors and DNA leading to the up-regulation of genes related to stress response and cell cycle arrest (23). In cancer, p53 is found silenced or mutated in 50 -55% of the all cases losing its function as a tumor suppressor (24). Mutations in p53 also correspond to poor prognosis and low response to chemotherapy (25).…”

Male-Specific Transcription Factor Occupancy Alone Does Not Account for Differential Methylation at Imprinted Genes in themouseGerm Cell Lineage

“…Interestingly, they include recognition sites for p53 and p63, both of which are present at the RNA level in male fetal germ cells. Although at present, it is not known whether the p53 protein is expressed and active, male germ cells are arrested in G1, consistent with p53 being active (Sperka et al 2012; Wang et al 2015). Some isoforms of p63 have been found to protect the germline by eliminating oocytes or male germ cells that have suffered DNA damage (Coutandin et al 2016).…”