A Mutation in the Carbohydrate Recognition Domain Drives a Phenotypic Switch in the Role of Galectin-7 in Prostate Cancer
| Autor: | Andrée-Anne Grosset, Bruno G. Leclerc, Yves St-Pierre, Marilyne Labrie, John Stagg, Louis Gaboury, Maria Claudia Vladoiu |
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| Přispěvatelé: | Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), This study was supported by the Canadian Institutes for Health Research (Grant No. MOP-89697) to YSP (http://www.cihr-irsc.gc.ca/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation ofthe manuscript. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
[SDV]Life Sciences [q-bio] Intracellular Space lcsh:Medicine Apoptosis Prostate cancer Mice MESH: Protein Structure Tertiary MESH: Mutant Proteins 0302 clinical medicine MESH: Structure-Activity Relationship Prostate MESH: Animals lcsh:Science 0303 health sciences Multidisciplinary Tissue microarray Transfection Protein Transport medicine.anatomical_structure Phenotype 030220 oncology & carcinogenesis MESH: Intracellular Space MESH: Galectins Research Article MESH: Protein Transport MESH: Mutation MESH: Cell Line Tumor Galectins [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Phenotype 03 medical and health sciences Structure-Activity Relationship Cell Line Tumor MESH: Cell Proliferation [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Animals Humans Neoplasm Invasiveness MESH: Mice 030304 developmental biology Galectin Cell Proliferation MESH: Humans MESH: Apoptosis lcsh:R Myoepithelial cell Cancer Prostatic Neoplasms MESH: Neoplasm Invasiveness medicine.disease eye diseases MESH: Male Protein Structure Tertiary Cell culture MESH: Prostatic Neoplasms Immunology Mutation Cancer research lcsh:Q Mutant Proteins |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2015, 10 (7), pp.e0131307. ⟨10.1371/journal.pone.0131307⟩ PLoS ONE, Vol 10, Iss 7, p e0131307 (2015) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0131307⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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