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

Journal of Cellular and Molecular Medicine
Divya ThomasPrakash Radhakrishnan

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 t...Continue Reading

References

Aug 1, 1992·American Journal of Clinical Pathology·S YonezawaE Sato
Jun 1, 1991·Gastroenterology·S ItzkowitzY S Kim
Feb 9, 2000·Journal of Hepato-biliary-pancreatic Surgery·A NanashimaH Ayabe
Aug 1, 2002·Proceedings of the National Academy of Sciences of the United States of America·Senitiroh Hakomori
May 22, 2003·The American Journal of Pathology·Sunfa Cheng, David H Lovett
Jul 19, 2005·Nature Reviews. Molecular Cell Biology·Barry M Gumbiner
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Jean Paul Thiery, Jonathan P Sleeman
May 19, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hideaki TsutsumidaMichael A Hollingsworth
Aug 8, 2007·Journal of Cellular Physiology·Honor HugoErik W Thompson
Jun 7, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Scott BidlingmaierBin Liu
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri
Jun 3, 2009·The Journal of Clinical Investigation·Michael Zeisberg, Eric G Neilson
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Feb 19, 2010·Journal of the National Cancer Institute·Zeshaan A RasheedWilliam Matsui
Jun 17, 2010·Journal of Biochemistry·Fengbiao ZhouYuanyan Wei
Apr 8, 2011·Neoplasia : an International Journal for Oncology Research·Jae-Hyun ParkYusuke Nakamura
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Leonardo Freire-de-LimaSen-Itiroh Hakomori
Mar 23, 2013·Cancer Cell·Jean Paul Thiery, Chwee Teck Lim
Apr 16, 2013·The EMBO Journal·Catharina SteentoftHenrik Clausen
Mar 13, 2014·The Journal of Biological Chemistry·Rajindra P AryalRichard D Cummings
Jan 1, 2012·Biomolecules·Sylvain JulienPhilippe Delannoy
Aug 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Prakash RadhakrishnanHans H Wandall
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Jan 27, 2015·Annual Review of Pathology·Sean R StowellRichard D Cummings
Mar 3, 2015·Advances in Cancer Research·Richard R Drake
May 30, 2015·Molecular Cancer·Bianca T HofmannGerrit Wolters-Eisfeld
Aug 14, 2015·Biomolecules·Liliana R LoureiroPaula A Videira
May 14, 2016·International Journal of Oncology·Lu ZhaoChristiane Josephine Bruns
May 31, 2016·Neoplasia : an International Journal for Oncology Research·Yunus Emre TarhanJae-Hyun Park
Jul 26, 2016·Frontiers in Oncology·Leonardo Marques da FonsecaMárcia Alves Marques Capella
Jul 7, 2017·Nature·Nicole M AielloBen Z Stanger
Jan 13, 2018·Nature Reviews. Cancer·Thomas BrabletzRobert A Weinberg
Feb 7, 2018·International Journal of Biological Macromolecules·Meritxell BalmañaRosa Peracaula
Feb 9, 2018·Oncotarget·Ninon VeryIkram El Yazidi-Belkoura
May 31, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Masaru NodaKoji Kono
Aug 22, 2018·Seminars in Cancer Biology·Patrick C Hermann, Bruno Sainz
May 12, 2019·FEBS Letters·Stefan MereiterCelso A Reis

❮ Previous
Next ❯

Citations

Nov 7, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Divya ThomasPrakash Radhakrishnan

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
FACS
RAP
PCR
flow cytometry
Flow
xenograft
glycosylation

Software Mentioned

ImageJ

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Related Papers

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Hui ZhangJide Wang
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaolin LiuBeihua Kong
© 2021 Meta ULC. All rights reserved