Truncated O-glycans promote epithelial-to-mesenchymal transition and stemness properties of pancreatic cancer cells

Divya Thomas, Satish Sagar, Thomas Caffrey, Paul M. Grandgenett, Prakash Radhakrishnan

Research output: Contribution to journalArticle

Abstract

Aberrant expression of Sialyl-Tn (STn) antigen correlates with poor prognosis and reduced patient survival. We demonstrated that expression of Tn and STn in pancreatic ductal adenocarcinoma (PDAC) is due to hypermethylation of Core 1 synthase specific molecular chaperone (COSMC) and enhanced the malignant properties of PDAC cells with an unknown mechanism. To explore the mechanism, we have genetically deleted COSMC in PDAC cells to express truncated O-glycans (SimpleCells, SC) which enhanced cell migration and invasion. Since epithelial-to-mesenchymal transition (EMT) play a vital role in metastasis, we have analysed the induction of EMT in SC cells. Expressions of the mesenchymal markers were significantly high in SC cells as compared to WT cells. Equally, we found reduced expressions of the epithelial markers in SC cells. Re-expression of COSMC in SC cells reversed the induction of EMT. In addition to this, we also observed an increased cancer stem cell population in SC cells. Furthermore, orthotopic implantation of T3M4 SC cells into athymic nude mice resulted in significantly larger tumours and reduced animal survival. Altogether, these results suggest that aberrant expression of truncated O-glycans in PDAC cells enhances the tumour aggressiveness through the induction of EMT and stemness properties.

Original languageEnglish (US)
Pages (from-to)6885-6896
Number of pages12
JournalJournal of cellular and molecular medicine
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2019

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Epithelial-Mesenchymal Transition
Pancreatic Neoplasms
Polysaccharides
Molecular Chaperones
Adenocarcinoma
Nude Mice
Neoplastic Stem Cells
Cell Movement
Neoplasms
Neoplasm Metastasis

Keywords

  • COSMC
  • EMT
  • PDAC
  • core-1 synthase
  • stem cells
  • truncated O-glycans

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Truncated O-glycans promote epithelial-to-mesenchymal transition and stemness properties of pancreatic cancer cells. / Thomas, Divya; Sagar, Satish; Caffrey, Thomas; Grandgenett, Paul M.; Radhakrishnan, Prakash.

In: Journal of cellular and molecular medicine, Vol. 23, No. 10, 01.10.2019, p. 6885-6896.

Research output: Contribution to journalArticle

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