Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses.
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.
Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 65653 Brno, Czech Republic. hrstka@mou.cz.
Joanna
J
Obacz
Silvia
S
Pastorekova
Borek
B
Vojtesek
Roman
R
Hrstka
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D004249:DNA Damage; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D051793:Hypoxia-Inducible Factor 1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53