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

Alessandro Genna, Stefanie Lapetina, Nikola Lukic, Shams Twafra, Tomer Meirson, Ved P. Sharma, John S. Condeelis, Hava Gil-Henn

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)375-395
Number of pages21
JournalJournal of Cell Biology
Volume217
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Cell Biology

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