Src kinase inhibition restores E-cadherin expression in dasatinib-sensitive pancreatic cancer cells

Oncotarget
Austin R DoschNagaraj S Nagathihalli

Abstract

The Src family of non-receptor tyrosine kinases are frequently activated in pancreatic ductal adenocarcinoma (PDAC), contributing to disease progression through downregulation of E-cadherin and induction of epithelial-to-mesenchymal transition (EMT). The purpose of this study was to examine the efficacy of Src kinase inhibition in restoring E-cadherin levels in PDAC. Immunohistochemical analysis of human PDAC samples showed Src activation is inversely correlated with E-cadherin levels. Protein and mRNA levels of E-cadherin, the gene expression of its various transcriptional repressors (Zeb1, Snail, Slug, LEF-1, TWIST), and changes in sub-cellular localization of E-cadherin/β-catenin in PDAC cells were characterized in response to treatment with the Src inhibitor, dasatinib (DST). DST repressed Slug mRNA expression, promoted E-cadherin transcription, and increased total and membranous E-cadherin/β-catenin levels in drug-sensitive PDAC cells (BxPC3 and SW1990), however no change was observed in drug-resistant PANC1 cells. BxPC3, PANC1, and MiaPaCa-2 flank tumor xenografts were treated with DST to examine changes in E-cadherin levels in vivo. Although DST inhibited Src phosphorylation in all xenograft models, E-cadherin levels wer...Continue Reading

References

Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
May 8, 2002·Nature Reviews. Molecular Cell Biology·M Angela Nieto
Jul 23, 2002·Nature Cell Biology·Egle AvizienyteMargaret C Frame
Apr 3, 2004·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Scott M Dehm, Keith Bonham
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
May 24, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C LouvetUNKNOWN GISCAD
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Faye M JohnsonNicholas J Donato
Dec 8, 2007·Biochemical and Biophysical Research Communications·Farhad VesunaVenu Raman
May 17, 2008·Cancer Research·Tamer T OnderRobert A Weinberg
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Oct 1, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·George D DemetriT R Jeffry Evans
Feb 10, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric B HauraGerold Bepler
Apr 27, 2010·Pancreas·Emily L DeerSean J Mulvihill
Aug 5, 2010·Molecular Cancer Therapeutics·Nagathihalli S NagarajNipun B Merchant
May 23, 2012·Seminars in Cancer Biology·M Angela Nieto, Amparo Cano
Nov 28, 2012·Investigational New Drugs·David S HongRazelle Kurzrock
Jan 22, 2013·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Apr 30, 2013·Gastroenterology·Marina Pasca di Magliano, Craig D Logsdon
Dec 22, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T R J EvansP J O'Dwyer
Jan 31, 2018·BioMed Research International·Shuai WangYu Ling Sun

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