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Pyk2 and FAK differentially regulate invadopodia formation and function in breast cancer cells

Authors :
Shams Twafra
Hava Gil-Henn
John S. Condeelis
Alessandro Genna
Ved P. Sharma
Stefanie Lapetina
Tomer Meirson
Nikola Lukic
Source :
The Journal of Cell Biology
Publication Year :
2017
Publisher :
Rockefeller University Press, 2017.

Abstract

The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but how it potentiates tumor cell invasiveness is unclear. Genna et al. find that Pyk2 and the closely related kinase FAK modulate breast cancer cell invasiveness by distinct mechanisms and coordinate the balance between focal adhesion–mediated migration and invadopodia-dependent extracellular matrix invasion.<br />The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but the mechanism by which it potentiates tumor cell invasiveness is unclear at present. Using high-throughput protein array screening and bioinformatic analysis, we identified cortactin as a novel substrate and interactor of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 colocalizes with cortactin to invadopodia of invasive breast cancer cells, where it mediates epidermal growth factor–induced cortactin tyrosine phosphorylation both directly and indirectly via Src-mediated Abl-related gene (Arg) activation, leading to actin polymerization in invadopodia, extracellular matrix degradation, and tumor cell invasion. Both Pyk2 and the closely related focal adhesion kinase (FAK) regulate tumor cell invasion, albeit via distinct mechanisms. Although Pyk2 regulates tumor cell invasion by controlling invadopodium-mediated functions, FAK controls invasiveness of tumor cells by regulating focal adhesion–mediated motility. Collectively, our findings identify Pyk2 as a unique mediator of invadopodium formation and function and also provide a novel insight into the mechanisms by which Pyk2 mediates tumor cell invasion.

Details

ISSN :
15408140 and 00219525
Volume :
217
Database :
OpenAIRE
Journal :
Journal of Cell Biology
Accession number :
edsair.doi.dedup.....4163e235cc790b7b1ba87b641d281908
Full Text :
https://doi.org/10.1083/jcb.201702184