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A Mutation in the Carbohydrate Recognition Domain Drives a Phenotypic Switch in the Role of Galectin-7 in Prostate Cancer

Labrie, Marilyne; Vladoiu, Maria Claudia; Leclerc, Bruno G; Grosset, Andrée-Anne; Gaboury, Louis; Stagg, John; St-Pierre, Yves (2015). A Mutation in the Carbohydrate Recognition Domain Drives a Phenotypic Switch in the Role of Galectin-7 in Prostate Cancer PLoS ONE , vol. 10 , nº 7. e0131307. DOI: 10.1371/journal.pone.0131307.

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Résumé

The observation that galectin-7 (gal-7) is specifically expressed in mammary myoepithelial (basal) cells prompted us to investigate whether this protein is expressed in the basal cells of other tissues. Given that breast and prostate cancer have remarkable underlying biological similarities and given the important roles of basal cells in prostate cancer, we examined the expression patterns and role of gal-7 in human prostate cancer. Using tissue microarray, we found that although gal-7 is readily expressed in basal cells in normal prostate tissue, it is downregulated in prostate cancer (PCa) cells. De novo expression of gal-7 in prostate cancer cells increases their sensitivity to apoptosis in response to etoposide and cisplatin. The assessment of a carbohydrate-recognition domain (CRD)-defective mutant form of gal-7 (R7S) showed that the ability of this protein to modulate apoptosis was independent of its CRD activity. This activity was also independent of its ability to translocate to the mitochondrial and nuclear compartments. However, CRD activity was necessary to inhibit the invasive behaviors of prostate cancer cells. In vivo, gal-7 overexpression in PCa cells led to a modest yet significant reduction in tumor size, while its CRD-defective mutant form significantly increased tumor growth compared to controls. Taken together, these results suggest that although de novo expression of gal-7 may be an interesting means of increasing the tumorigenic phenotypes of PCa cells, alterations in the CRD activity of this protein drive a phenotypic switch in its role in PCa cells. This CRD-independent activity represents a paradigm shift in our understanding of the functions of galectin. The R74S model will be useful to distinguish CRD-dependent and CRD-independent functions of gal-7 in cancer progression.

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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 mars 2016 21:28
Dernière modification: 11 janv. 2017 20:50
URI: http://espace.inrs.ca/id/eprint/3207

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