Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas

Oncotarget
Laurence VeraciniE Van Obberghen-Schilling

Abstract

EGF receptor (EGFR) overexpression is thought to drive head and neck carcinogenesis however clinical responses to EGFR-targeting agents have been modest and alternate targets are actively sought to improve results. Src family kinases (SFKs), reported to act downstream of EGFR are among the alternative targets for which increased expression or activity in epithelial tumors is commonly associated to the dissolution of E-cadherin-based junctions and acquisition of a mesenchymal-like phenotype. Robust expression of total and activated Src was observed in advanced stage head and neck tumors (N=60) and in head and neck squamous cell carcinoma lines. In cultured cancer cells Src co-localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419 was both constitutive and independent of EGFR activation. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes. These findings reveal an EGFR-independent role for SFKs in the maintenance of intercellular junctions, which likely contributes to the cohesive invasion E-cadherin-positive cells in advanced tumors. Further, they highlight the ...Continue Reading

References

Apr 1, 1987·Molecular and Cellular Biology·S L Warren, W J Nelson
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·M C MaaS J Parsons
Jun 25, 1998·The Journal of Cell Biology·E CalauttiG Paolo Dotto
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·D A TiceS J Parsons
Nov 14, 2000·Molecular and Cellular Biology·R A BlakeS A Courtneidge
Nov 27, 2001·Science·E CukiermanK M Yamada
May 29, 2003·The Journal of Biological Chemistry·Sichuan XiJennifer Rubin Grandis
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Michael M Kim, Joseph A Califano
Aug 16, 2005·Current Opinion in Cell Biology·Egle Avizienyte, Margaret C Frame
Feb 10, 2006·The New England Journal of Medicine·James A BonnerK Kian Ang
Sep 5, 2006·Cancer Research·Jason J Christiansen, Ayyappan K Rajasekaran
Oct 6, 2006·Expert Review of Anticancer Therapy·Igor AstsaturovPaul Harari
Jun 8, 2007·Molecular Biology of the Cell·Robert W McLachlanAlpha S Yap
Oct 27, 2007·Experimental Cell Research·Akiko OnishiRandall H Kramer
Jun 12, 2008·Seminars in Oncology·Ann Marie Egloff, Jennifer R Grandis
Jul 16, 2008·Current Opinion in Pharmacology·Valerie G Brunton, Margaret C Frame
Jun 24, 2009·Nature Reviews. Molecular Cell Biology·Peter Friedl, Darren Gilmour
Jan 15, 2010·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Markus Lindauer, Andreas Hochhaus
May 18, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Stephen Y Lai, Faye M Johnson
May 28, 2010·Journal of Cancer Science & Therapy·Amanda Gatesman AmmerScott A Weed
Jan 27, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ann Marie Egloff, Jennifer R Grandis
Nov 29, 2011·Cell·Peter Friedl, Stephanie Alexander
Dec 14, 2011·Trends in Pharmacological Sciences·Siyuan Zhang, Dihua Yu
Jan 10, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juliette ThariatEllen Van Obberghen-Schilling
Aug 3, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juliette ThariatGérard Milano
Nov 16, 2012·Investigational New Drugs·Tara C GangadharThomas F Gajewski
Dec 6, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura P StabileJennifer R Grandis

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Citations

Oct 27, 2017·Annual Review of Pathology·Nicolo RiggiIvan Stamenkovic
May 7, 2016·Cellular and Molecular Life Sciences : CMLS·Peter Coopman, Alexandre Djiane
Jan 20, 2017·Nature Communications·Sandeep GopalEllen Van Obberghen-Schilling
Aug 20, 2017·The Journal of Biological Chemistry·Jayshree MishraNarendra Kumar
Jan 29, 2016·International Journal of Molecular Medicine·Xue WuDahai Hu
Aug 8, 2019·Molecular Biology of the Cell·Abhinava K MishraDenise J Montell
Sep 29, 2018·F1000Research·Jessica L ChittyPaul Timpson
Apr 6, 2021·Mediators of Inflammation·Narendra KumarJayshree Mishra

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Methods Mentioned

BETA
co-immunoprecipitation
transfection
xenograft
FCS
electrophoresis

Clinical Trials Mentioned

NCT00169221

Software Mentioned

Axiovision
MatLab
MetaMorph

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