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Article

The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression

1
Department of Molecular Medicine, Université Laval, Québec, QC G1V 0A6, Canada
2
CHU de Québec Research Center, Oncology axis Québec, Québec, QC G1V 4G2, Canada
3
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
4
CHU de Québec Research Center, Endocrinology and Nephrology axis Québec, Québec, QC G1V 4G2, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2264; https://doi.org/10.3390/ijms20092264
Received: 18 April 2019 / Revised: 3 May 2019 / Accepted: 4 May 2019 / Published: 8 May 2019
Epithelial ovarian cancer (EOC) represents the most lethal gynecologic malignancy; a better understanding of the molecular mechanisms associated with EOC etiology could substantially improve EOC management. Aberrant O-glycosylation in cancer is attributed to alteration of N-acetylgalactosaminyltransferases (GalNAc-Ts). Reports suggest a genetic and functional redundancy between GalNAc-Ts, and our previous data are indicative of an induction of GALNT6 expression upon GALNT3 suppression in EOC cells. We performed single GALNT3 and double GALNT3/T6 suppression in EOC cells, using a combination of the CRISPR-Cas9 system and shRNA-mediated gene silencing. The effect of single GALNT3 and double GALNT3/T6 inhibition was monitored both in vitro (on EOC cells roliferation, migration, and invasion) and in vivo (on tumor formation and survival of experimental animals). We confirmed that GALNT3 gene ablation leads to strong and rather compensatory GALNT6 upregulation in EOC cells. Moreover, double GALNT3/T6 suppression was significantly associated with stronger inhibitory effects on EOC cell proliferation, migration, and invasion, and accordingly displayed a significant increase in animal survival rates compared with GALNT3-ablated and control (Ctrl) EOC cells. Our data suggest a possible functional redundancy of GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective of using both these enzymes as novel EOC biomarkers and/or therapeutic targets. View Full-Text
Keywords: epithelial ovarian cancer; O-glycosylation; N-acetylgalactosaminyltransferases; VVA lectin; microarrays; intraperitoneal tumor formation epithelial ovarian cancer; O-glycosylation; N-acetylgalactosaminyltransferases; VVA lectin; microarrays; intraperitoneal tumor formation
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MDPI and ACS Style

Sheta, R.; Bachvarova, M.; Macdonald, E.; Gobeil, S.; Vanderhyden, B.; Bachvarov, D. The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression. Int. J. Mol. Sci. 2019, 20, 2264. https://doi.org/10.3390/ijms20092264

AMA Style

Sheta R, Bachvarova M, Macdonald E, Gobeil S, Vanderhyden B, Bachvarov D. The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression. International Journal of Molecular Sciences. 2019; 20(9):2264. https://doi.org/10.3390/ijms20092264

Chicago/Turabian Style

Sheta, Razan, Magdalena Bachvarova, Elizabeth Macdonald, Stephane Gobeil, Barbara Vanderhyden, and Dimcho Bachvarov. 2019. "The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression" International Journal of Molecular Sciences 20, no. 9: 2264. https://doi.org/10.3390/ijms20092264

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