The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells

Christopher A. Lipinski, Nhan Tran, Emmanuel Menashi, Carole Rohl, Jean Kloss, R. Curtis Bay, Michael E. Berens, Joseph C Loftus

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Glioblastoma multiforme is extraordinarily aggressive due to the propensity of cells to migrate away from the tumor core into the surrounding normal brain. In this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2) and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2 stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell migration and stimulated cell cycle progression. Pyk2 autophosphorylation was necessary, but not sufficient, to stimulate cellular migration. The N-terminal domain of Pyk2 is required for stimulation of migration as an N-terminally deleted variant of Pyk2 failed to stimulate migration, whereas expression of an autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C-terminal domain of Pyk2 with the corresponding domain of FAK simulated cell migration as effectively as wild-type Pyk2; however, substitution of the N-terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing of Pyk2 expression by RNA interference significantly inhibited glioma migration. Cell migration was restored on reexpression of Pyk2, but expression of FAK in Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a central role in the migratory behavior of glioblastomas.

Original languageEnglish (US)
Pages (from-to)435-445
Number of pages11
JournalNeoplasia
Volume7
Issue number5
DOIs
StatePublished - May 2005

Fingerprint

Focal Adhesion Kinase 2
Glioma
Protein-Tyrosine Kinases
Cell Movement
Glioblastoma

Keywords

  • Focal adhesion kinase
  • Glioma
  • Invasion
  • Migration
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research

Cite this

The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells. / Lipinski, Christopher A.; Tran, Nhan; Menashi, Emmanuel; Rohl, Carole; Kloss, Jean; Bay, R. Curtis; Berens, Michael E.; Loftus, Joseph C.

In: Neoplasia, Vol. 7, No. 5, 05.2005, p. 435-445.

Research output: Contribution to journalArticle

Lipinski, CA, Tran, N, Menashi, E, Rohl, C, Kloss, J, Bay, RC, Berens, ME & Loftus, JC 2005, 'The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells', Neoplasia, vol. 7, no. 5, pp. 435-445. https://doi.org/10.1593/neo.04712
Lipinski CA, Tran N, Menashi E, Rohl C, Kloss J, Bay RC et al. The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells. Neoplasia. 2005 May;7(5):435-445. https://doi.org/10.1593/neo.04712
Lipinski, Christopher A. ; Tran, Nhan ; Menashi, Emmanuel ; Rohl, Carole ; Kloss, Jean ; Bay, R. Curtis ; Berens, Michael E. ; Loftus, Joseph C. / The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells. In: Neoplasia. 2005 ; Vol. 7, No. 5. pp. 435-445.
@article{cc61805f6cdb4cfdbf9af8f1af9d5c68,
title = "The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells",
abstract = "Glioblastoma multiforme is extraordinarily aggressive due to the propensity of cells to migrate away from the tumor core into the surrounding normal brain. In this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2) and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2 stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell migration and stimulated cell cycle progression. Pyk2 autophosphorylation was necessary, but not sufficient, to stimulate cellular migration. The N-terminal domain of Pyk2 is required for stimulation of migration as an N-terminally deleted variant of Pyk2 failed to stimulate migration, whereas expression of an autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C-terminal domain of Pyk2 with the corresponding domain of FAK simulated cell migration as effectively as wild-type Pyk2; however, substitution of the N-terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing of Pyk2 expression by RNA interference significantly inhibited glioma migration. Cell migration was restored on reexpression of Pyk2, but expression of FAK in Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a central role in the migratory behavior of glioblastomas.",
keywords = "Focal adhesion kinase, Glioma, Invasion, Migration, Tyrosine kinase",
author = "Lipinski, {Christopher A.} and Nhan Tran and Emmanuel Menashi and Carole Rohl and Jean Kloss and Bay, {R. Curtis} and Berens, {Michael E.} and Loftus, {Joseph C}",
year = "2005",
month = "5",
doi = "10.1593/neo.04712",
language = "English (US)",
volume = "7",
pages = "435--445",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - The tyrosine kinase Pyk2 promotes migration and invasion of glioma cells

AU - Lipinski, Christopher A.

AU - Tran, Nhan

AU - Menashi, Emmanuel

AU - Rohl, Carole

AU - Kloss, Jean

AU - Bay, R. Curtis

AU - Berens, Michael E.

AU - Loftus, Joseph C

PY - 2005/5

Y1 - 2005/5

N2 - Glioblastoma multiforme is extraordinarily aggressive due to the propensity of cells to migrate away from the tumor core into the surrounding normal brain. In this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2) and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2 stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell migration and stimulated cell cycle progression. Pyk2 autophosphorylation was necessary, but not sufficient, to stimulate cellular migration. The N-terminal domain of Pyk2 is required for stimulation of migration as an N-terminally deleted variant of Pyk2 failed to stimulate migration, whereas expression of an autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C-terminal domain of Pyk2 with the corresponding domain of FAK simulated cell migration as effectively as wild-type Pyk2; however, substitution of the N-terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing of Pyk2 expression by RNA interference significantly inhibited glioma migration. Cell migration was restored on reexpression of Pyk2, but expression of FAK in Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a central role in the migratory behavior of glioblastomas.

AB - Glioblastoma multiforme is extraordinarily aggressive due to the propensity of cells to migrate away from the tumor core into the surrounding normal brain. In this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2) and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2 stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell migration and stimulated cell cycle progression. Pyk2 autophosphorylation was necessary, but not sufficient, to stimulate cellular migration. The N-terminal domain of Pyk2 is required for stimulation of migration as an N-terminally deleted variant of Pyk2 failed to stimulate migration, whereas expression of an autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C-terminal domain of Pyk2 with the corresponding domain of FAK simulated cell migration as effectively as wild-type Pyk2; however, substitution of the N-terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing of Pyk2 expression by RNA interference significantly inhibited glioma migration. Cell migration was restored on reexpression of Pyk2, but expression of FAK in Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a central role in the migratory behavior of glioblastomas.

KW - Focal adhesion kinase

KW - Glioma

KW - Invasion

KW - Migration

KW - Tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=20344393365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344393365&partnerID=8YFLogxK

U2 - 10.1593/neo.04712

DO - 10.1593/neo.04712

M3 - Article

C2 - 15967096

AN - SCOPUS:20344393365

VL - 7

SP - 435

EP - 445

JO - Neoplasia

JF - Neoplasia

SN - 1522-8002

IS - 5

ER -