The circadian clock and the hypoxic response pathway in kidney cancer
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The most frequent malignant tumor of the kidney in adults is represented by renal cell carcinoma characterized by high lethality related to presence of metastatic disease at the time of diagnosis. The main characteristic molecular feature of most sporadic renal cell carcinomas is the mutation of the tumor suppressor gene encoding the von Hippel-Lindau protein, with alteration of regulated pathways and activation of hypoxia-inducible transcription factors. Hypoxia-inducible transcription factors are transcriptional regulators of genes controlling mammalian oxygen homeostasis, energy metabolism, neovascularisation, internal pH, cell survival, and migration and are considered powerful promoters of tumor growth. Tight interrelationships have been evidenced between hypoxic response pathway and circadian pathway. Severe deregulation of genes involved in the circadian clock circuitry and response to hypoxia has been found in patients affected by kidney cancer, influencing the process of carcinogenesis, as well as disease progression and outcome. The study of alterations of clock gene expression and hypoxia correlated pathway in kidney cancer may promote the comprehension of pathophysiological mechanisms involved in renal cell carcinoma onset and evolution and may help to exploit more effective therapeutic approaches.
KeywordsKidney Cancer Clock gene Circadian Rhythm Hypoxia
We apologize for not citing all pertinent references due to space limitations. The study was supported by the “5 × 1,000” voluntary contribution by a grant (MV) from AIRC (MFAG-AIRC 2012–13419), and by “Italian Ministry of Health” grant (GM) RC1203ME46 and RC1302ME31 through Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo (FG), Italy.
Conflicts of interest
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