Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses

Abstract

Abnormal rates of growth together with metastatic potential and lack of susceptibility to cellular signals leading to apoptosis are widely investigated characteristics of tumors that develop via genetic or epigenetic mechanisms. Moreover, in the growing tumor, cells are exposed to insufficient nutrient supply, low oxygen availability (hypoxia) and/or reactive oxygen species. These physiological stresses force them to switch into more adaptable and aggressive phenotypes. This paper summarizes the role of two key mediators of cellular stress responses, namely p53 and HIF, which significantly affect cancer progression and compromise treatment outcomes. Furthermore, it describes cross-talk between these factors.

HIF-1α promotes autophagic proteolysis of Dicer and enhances tumor metastasis

“…Nevertheless, there is a paucity of evidence showing that ubiquitination of Dicer correlates with autophagy degradation and its E3 ligase remains unidentified (55). In the present study, we between HIF-1α and p53 pathways regulates tumor growth at different stages of cancer progression (51). Therefore, in contrast with tumor-suppressive p53, which interacts with the Drosha complex and enhances the processing of primary miRNA (52), the oncogenic HIF-1α acts as a gatekeeper for cancer cells, thus preventing the maturation of pre-miRNA by Dicer and resulting in fine-tuning the balance modulating cancer progression.…”

Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1

“…However, the precise relationship of HIF-1 and p53 is still very complicated and unclear. The interaction between HIF-1 and p53 has been previously and comprehensively reviewed 75 . Based on the above-mentioned information, apoptosis or cell survival in hypoxic regions of tumors probably depends on the type of tumor and the presence or absence of genetic alterations that affect the balance between pro-apoptotic and anti-apoptotic roles of hypoxia-induced factors 76 .…”

DNA damage response upon environmental contaminants: An exhausting work for genomic integrity

“…In tumour environment in which glucose is elevated, there is no systematic effect on p53-regulated DDR [15]. Thus p53 activity, by limiting Warburg effect when non-mutated, antagonizes HIF1α activity [19].…”