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

  • Authors:
    • Louisa Rafa
    • Anne-Frédérique Dessein
    • Louise Devisme
    • David Buob
    • Stéphanie Truant
    • Nicole Porchet
    • Guillemette Huet
    • Marie-Pierre Buisine
    • Thécla Lesuffleur
  • View Affiliations

  • Published online on: March 1, 2010     https://doi.org/10.3892/ijo_00000544
  • Pages: 689-698
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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, REG4 expression was found to be increased in tissues harboring proliferation and migration properties such as the developing intestine and tissues from inflammatory bowel disease, hyperplastic polyps, adenoma and colorectal cancers. In various situations, REG4 expression was not confined to proliferating cells, regenerating cells or cells of the invasive front of metastatic tumors, suggesting that extracellular REG4 may act on epithelial cells in a paracrine manner. Altogether, our results indicate that REG4 is a multifunctional secreted protein which acts on colorectal cancer cells in an autocrine and paracrine manner. According to its biological functions and tissue expression, REG4 may play an important role in the development and progression of colorectal cancer, as well as in intestinal morphogenesis and epithelium restitution.

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March 2010
Volume 36 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Rafa L, Dessein A, Devisme L, Buob D, Truant S, Porchet N, Huet G, Buisine M and Lesuffleur T: REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. Int J Oncol 36: 689-698, 2010.
APA
Rafa, L., Dessein, A., Devisme, L., Buob, D., Truant, S., Porchet, N. ... Lesuffleur, T. (2010). REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. International Journal of Oncology, 36, 689-698. https://doi.org/10.3892/ijo_00000544
MLA
Rafa, L., Dessein, A., Devisme, L., Buob, D., Truant, S., Porchet, N., Huet, G., Buisine, M., Lesuffleur, T."REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells". International Journal of Oncology 36.3 (2010): 689-698.
Chicago
Rafa, L., Dessein, A., Devisme, L., Buob, D., Truant, S., Porchet, N., Huet, G., Buisine, M., Lesuffleur, T."REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells". International Journal of Oncology 36, no. 3 (2010): 689-698. https://doi.org/10.3892/ijo_00000544