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The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis.

Publication ,  Journal Article
Kelly, P; Moeller, BJ; Juneja, J; Booden, MA; Der, CJ; Daaka, Y; Dewhirst, MW; Fields, TA; Casey, PJ
Published in: Proc Natl Acad Sci U S A
May 23, 2006

Although the prognosis for patients with early-stage breast cancer has improved, the therapeutic options for patients with locally advanced and metastatic disease are limited. To improve the treatment of these patients, the molecular mechanisms underlying breast cancer invasion and metastasis must be understood. In this study, we report that signaling through the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) promotes breast cancer cell invasion. Moreover, we demonstrate that inhibition of G12 signaling reduces the metastatic dissemination of breast cancer cells in vivo. Finally, we demonstrate that the expression of Galpha12 is significantly up-regulated in the earliest stages of breast cancer, implying that amplification of G12 signaling may be an early event in breast cancer progression. Taken together, these observations identify the G12 family proteins as important regulators of breast cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced patient morbidity and mortality.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 23, 2006

Volume

103

Issue

21

Start / End Page

8173 / 8178

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Retroviridae
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Mice
  • Humans
  • Gene Expression Regulation
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Cadherins
 

Citation

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Kelly, P., Moeller, B. J., Juneja, J., Booden, M. A., Der, C. J., Daaka, Y., … Casey, P. J. (2006). The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A, 103(21), 8173–8178. https://doi.org/10.1073/pnas.0510254103
Kelly, Patrick, Benjamin J. Moeller, Juhi Juneja, Michelle A. Booden, Channing J. Der, Yehia Daaka, Mark W. Dewhirst, Timothy A. Fields, and Patrick J. Casey. “The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis.Proc Natl Acad Sci U S A 103, no. 21 (May 23, 2006): 8173–78. https://doi.org/10.1073/pnas.0510254103.
Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, et al. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8173–8.
Kelly, Patrick, et al. “The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis.Proc Natl Acad Sci U S A, vol. 103, no. 21, May 2006, pp. 8173–78. Pubmed, doi:10.1073/pnas.0510254103.
Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8173–8178.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 23, 2006

Volume

103

Issue

21

Start / End Page

8173 / 8178

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Retroviridae
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Mice
  • Humans
  • Gene Expression Regulation
  • GTP-Binding Protein alpha Subunits, G12-G13
  • Cadherins