Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells

Marco Genua, Shi Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonino Belfiore, Renato V. Iozzo, Andrea Morrione

Research output: Contribution to journalArticle

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Abstract

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in bladder cancer has not been established. In this study we demonstrate that FAK was not required for IGF-IR-dependent signaling and motility of invasive urothelial carcinoma cells. On the contrary, Pyk2, which was strongly activated by IGF-I, was critical for IGF-IR-dependent motility and invasion and regulated IGF-I-dependent activation of the Akt and MAPK pathways. Using immunofluorescence and AQUA analysis we further discovered that Pyk2 was overexpressed in bladder cancer tissues as compared to normal tissue controls. Significantly, in urothelial carcinoma tissues there was increased Pyk2 localization in the nuclei as compared to normal tissue controls. These results provide the first evidence of a specific Pyk2 activity in regulating IGF-IR-dependent motility and invasion of bladder cancer cells suggesting that Pyk2 and the IGF-IR may play a critical role in the invasive phenotype in urothelial neoplasia. In addition, Pyk2 and the IGF-IR may serve as novel biomarkers with diagnostic and prognostic significance in bladder cancer.

Original languageEnglish
Article numbere40148
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 28 2012

Fingerprint

Focal Adhesion Kinase 2
cell invasion
insulin-like growth factor I
Insulin-Like Growth Factor I
cell movement
carcinoma
Cell Movement
tyrosine
proline
phosphotransferases (kinases)
Cells
Urinary Bladder Neoplasms
non-specific protein-tyrosine kinase
Carcinoma
Focal Adhesion Protein-Tyrosine Kinases
Tissue
Paxillin
cells
Chemical activation
Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genua, M., Xu, S. Q., Buraschi, S., Peiper, S. C., Gomella, L. G., Belfiore, A., ... Morrione, A. (2012). Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells. PLoS One, 7(6), [e40148]. https://doi.org/10.1371/journal.pone.0040148

Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells. / Genua, Marco; Xu, Shi Qiong; Buraschi, Simone; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea.

In: PLoS One, Vol. 7, No. 6, e40148, 28.06.2012.

Research output: Contribution to journalArticle

Genua, M, Xu, SQ, Buraschi, S, Peiper, SC, Gomella, LG, Belfiore, A, Iozzo, RV & Morrione, A 2012, 'Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells', PLoS One, vol. 7, no. 6, e40148. https://doi.org/10.1371/journal.pone.0040148
Genua, Marco ; Xu, Shi Qiong ; Buraschi, Simone ; Peiper, Stephen C. ; Gomella, Leonard G. ; Belfiore, Antonino ; Iozzo, Renato V. ; Morrione, Andrea. / Proline-rich tyrosine kinase 2 (Pyk2) regulates IGF-I-induced cell motility and invasion of urothelial carcinoma cells. In: PLoS One. 2012 ; Vol. 7, No. 6.
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