PMID: 20126989Feb 4, 2010Paper

REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells

International Journal of Oncology
Louisa RafaThécla Lesuffleur

Abstract

REG4, the latest member of the regenerating gene family, is overexpressed in inflammatory bowel diseases and gastrointestinal carcinomas. To date, its pathophysiologic role has not been well established. Using HT-29 models, we previously identified REG4 as being overexpressed in colorectal tumor cells displaying a drug-resistance phenotype; some also displayed invasive properties. Thus, we investigated the potential functions of REG4 in biological processes involved in colorectal tumor progression such as cell proliferation, migration and invasion. Colon cancer cells secreting REG4 (HT29-5M21, HT29-5F7 and HT29/REG4-8) or not (HT-29, HT29/CT1 and Caco-2/TC7) were used to analyze the autocrine and paracrine effects of REG4. REG4 was continuously secreted into the culture medium of colon cancer cells. REG4 stimulated cell growth in a paracrine manner after 24 h of treatment. Notably, REG4 promoted migration and invasion of tumor cells in both an autocrine and paracrine manner, and these effects were significantly decreased by concomitant treatment with an anti-REG4 antibody. Using pharmacological inhibitors, we showed that PI3K/Akt, PKAs, PKCs and Rho-like GTPases, but not MAPK, are involved in REG4 invasion signals. In addition,...Continue Reading

Citations

Jul 25, 2012·World Journal of Gastroenterology : WJG·Masakatsu Numata, Takashi Oshima
Mar 23, 2013·Cell and Tissue Research·Atle van Beelen GranlundArne Kristian Sandvik
Dec 20, 2015·Molecular and Cellular Endocrinology·Lu-Ting YuChen Luo
Mar 19, 2013·Regulatory Peptides·Kukka Heiskala, Leif C Andersson
Dec 4, 2012·Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology·Fang Du, Zhen-Wei Yao
Mar 30, 2011·International Journal of Cancer. Journal International Du Cancer·Kathryn VanderlaagMary J Janatpour
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Jul 16, 2014·Pathology, Research and Practice·Bianka BojkováKarol Kajo
Aug 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nobuo SasakiHans Clevers
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