Mar 12, 2020

Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44

Cancer Management and Research
Tan DuTao Wen

Abstract

Breast cancer remains the most lethal malignancy in women worldwide. Aberrant O-glycosylation is closely related to many human diseases, including breast carcinoma; however, its precise role in cancer development is insufficiently understood. Cosmc is an endoplasmic reticulum-localized chaperone that regulates the O-glycosylation of proteins. Cosmc dysfunction results in inactive T-synthase and expression of truncated O-glycans such as Tn antigen. Here we investigated the impact of Cosmc disruption-mediated aberrant O-glycosylation on breast cancer cell development through in vitro and in vivo experiments. We deleted the Cosmc gene in two breast cancer cell lines (MCF7, T47D) using the CRISPR/Cas-9 system and then measured the expression levels of Tn antigen. The proliferation of Tn-positive cells was examined by RTCA, colony formation and in vivo experiments. The effects of Cosmc deficiency on glycoprotein CD44 and MAPK pathway were also determined. Both in vitro and in vivo studies showed that Cosmc deficiency markedly suppressed breast cancer cell growth compared with the corresponding controls. Mechanistically, Cosmc disruption impaired the protein expression of CD44 and the associated MAPK signaling pathway; the latter pla...Continue Reading

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Mentioned in this Paper

Lipid Glycosylation
Breast Cancer Cell
Colony (Cells or Organisms)
Woman
Malignant Neoplasms
CD44 gene
CD44
Protein Expression
Nitric Oxide Synthase
Tumor Cells, Malignant

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