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Pyk2 and FAK differentially regulate invadopodia formation and function in breast cancer cells
- 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.
- Subjects :
- 0301 basic medicine
Podosome
Breast Neoplasms
macromolecular substances
Biology
Article
Focal adhesion
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Cell Line, Tumor
Animals
Humans
Neoplasm Invasiveness
Tyrosine
Research Articles
Focal Adhesions
Tyrosine phosphorylation
Cell Biology
High-Throughput Screening Assays
Rats
Cell biology
Focal Adhesion Kinase 2
030104 developmental biology
chemistry
Tyrosine kinase 2
Focal Adhesion Kinase 1
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Podosomes
Invadopodia
biology.protein
Female
Cortactin
Tyrosine kinase
Subjects
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