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G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion.

Publication ,  Journal Article
Juneja, J; Cushman, I; Casey, PJ
Published in: PLoS One
2011

Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JNK activation as well as the ability of breast cancer cells to invade a reconstituted basement membrane. Furthermore, expression of dominant-negative Rho or treatment of cells with an inhibitor of the Rho kinase, ROCK, reduces G12-induced JNK and c-Jun activation, and ROCK inhibitor treatment also inhibits G12-induced cellular invasion. JNK knockdown or ROCK inhibitor treatment has no effect on activation of Rho by G12. Taken together, our data indicate that JNK activation is required for G12-induced invasion of breast cancer cells and that JNK is downstream of Rho and ROCK on this pathway. This study implicates a G12-stimulated mitogen-activated protein kinase cascade in cancer cell invasion, and supports a role for JNK in cancer progression.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

11

Start / End Page

e26085

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho-Associated Kinases
  • Signal Transduction
  • Phosphorylation
  • Neoplasm Invasiveness
  • JNK Mitogen-Activated Protein Kinases
  • Humans
  • General Science & Technology
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Female
 

Citation

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Juneja, J., Cushman, I., & Casey, P. J. (2011). G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion. PLoS One, 6(11), e26085. https://doi.org/10.1371/journal.pone.0026085
Juneja, Juhi, Ian Cushman, and Patrick J. Casey. “G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion.PLoS One 6, no. 11 (2011): e26085. https://doi.org/10.1371/journal.pone.0026085.
Juneja J, Cushman I, Casey PJ. G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion. PLoS One. 2011;6(11):e26085.
Juneja, Juhi, et al. “G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion.PLoS One, vol. 6, no. 11, 2011, p. e26085. Pubmed, doi:10.1371/journal.pone.0026085.
Juneja J, Cushman I, Casey PJ. G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion. PLoS One. 2011;6(11):e26085.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

11

Start / End Page

e26085

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho-Associated Kinases
  • Signal Transduction
  • Phosphorylation
  • Neoplasm Invasiveness
  • JNK Mitogen-Activated Protein Kinases
  • Humans
  • General Science & Technology
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Female