Mazzoccoli G, Vinciguerra M, Papa G, Piepoli A. Circadian clock circuitry in colorectal cancer. World J Gastroenterol 2014; 20(15): 4197-4207 [PMID: 24764658 DOI: 10.3748/wjg.v20.i15.4197]
Corresponding Author of This Article
Gianluigi Mazzoccoli, MD, Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Cappuccini Avenue, 71013 San Giovanni Rotondo Foggia, Italy. g.mazzoccoli@operapadrepio.it
Research Domain of This Article
Medicine, General & Internal
Article-Type of This Article
Topic Highlight
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World J Gastroenterol. Apr 21, 2014; 20(15): 4197-4207 Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4197
Circadian clock circuitry in colorectal cancer
Gianluigi Mazzoccoli, Manlio Vinciguerra, Gennaro Papa, Ada Piepoli
Gianluigi Mazzoccoli, Manlio Vinciguerra, Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo Foggia, Italy
Manlio Vinciguerra, Istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST), 90100 Palermo, Italy
Manlio Vinciguerra, Division of Medicine, Royal Free Campus, Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom
Gennaro Papa, Department of Surgical Sciences, Division of Urology, University of Chieti, 66100 Chieti, Italy
Ada Piepoli, Department of Medical Sciences, Research Laboratory and Division of Gastroenterology, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo Foggia, Italy
Author contributions: Mazzoccoli G and Vinciguerra M contributed equally to this work; Mazzoccoli G and Piepoli A conceived the review article; Papa G performed the literature mining; Mazzoccoli G, Vinciguerra M, Papa G and Piepoli A wrote the paper.
Supported by The “5x1000” voluntary contribution and by a grant to GM from the Italian Ministry of Health 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, Nos. RC1203ME46 and RC1302ME31; by a grant to AP from the Italian Ministry of Health through Department of Medical Sciences, Division of Gastroenterology and Research Laboratory, Nos. RC1203GA55 and RC1203GA56; and by a grant to MV from AIRC, No. MFAG-AIRC2012-13419
Correspondence to: Gianluigi Mazzoccoli, MD, Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Cappuccini Avenue, 71013 San Giovanni Rotondo Foggia, Italy. g.mazzoccoli@operapadrepio.it
Telephone: +39-882-410275 Fax: +39-882-410275
Received: September 9, 2013 Revised: January 6, 2014 Accepted: January 19, 2014 Published online: April 21, 2014
Abstract
Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
Core tip: The biological clock drives crucial cell processes, such as growth, proliferation, differentiation and apoptosis, controls metabolic pathways, and regulates tissue functions and behavioral cycles. Derangement of these phenomena is involved in colorectal carcinogenesis. The circadian clock circuitry is a leading actor in physiological regulation, a drawn in bystander in colorectal tumorigenesis, and a possible therapeutic target.
