β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells

Timothy T. Li, Mistre Alemayehu, Adel I. Aziziyeh, Cynthia Pape, Macarena Pampillo, Lynne Marie Postovit, Gordon Mills, Andy V. Babwah, Moshmi Bhattacharya

Research output: Contribution to journalArticle

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Abstract

The lipid mediator lysophosphatidic acid (LPA) plays a role in cancer progression and signals via specific G protein-coupled receptors, LPA1-3.LPA has been shown to enhance the metastasis of breast carcinoma cells to bone. However, the mechanisms by which LPA receptors regulate breast cancer cell migration and invasion remain unclear. Breast cancer cell proliferation has been shown to be stimulated by Ral GTPases, amember of the Ras superfamily. Ral activity can be regulated by the multifunctional protein â-arrestin.We now show that HS578T and MDA-MB-231 breast cancer cells and MDA-MB-435 melanoma cells have higher expression of â-arrestin 1 mRNA compared with the nontumorigenic mammary MCF-10A cells.Moreover, we found that the mRNA levels of LPA1, LPA2, â-arrestin 2, and Ral GTPases are elevated in the advanced stages of breast cancer.LPA stimulates the migration and invasion of MDA-MB-231 cells, but not of MCF-10A cells, and this is mediated by pertussis toxin-sensitive G proteins and LPA1. However, ectopic expression of LPA1 in MCF-10A cells caused these cells to acquire an invasive phenotype.Ge ne knockdown of either â-arrestin or Ral proteins significantly impaired LPA-stimulated migration and invasion.Th us, our data show a novel role for â-arrestin/Ral signaling in mediating LPA-induced breast cancer cell migration and invasion, two important processes in metastasis.

Original languageEnglish (US)
Pages (from-to)1064-1077
Number of pages14
JournalMolecular Cancer Research
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Fingerprint

Arrestin
Breast Neoplasms
ral GTP-Binding Proteins
Cell Movement
Lysophosphatidic Acid Receptors
Neoplasm Metastasis
ras Proteins
Messenger RNA
lysophosphatidic acid
GTP Phosphohydrolases
Pertussis Toxin
G-Protein-Coupled Receptors
GTP-Binding Proteins
Melanoma
Breast
Cell Proliferation
Phenotype
Lipids
Bone and Bones

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Li, T. T., Alemayehu, M., Aziziyeh, A. I., Pape, C., Pampillo, M., Postovit, L. M., ... Bhattacharya, M. (2009). β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells. Molecular Cancer Research, 7(7), 1064-1077. https://doi.org/10.1158/1541-7786.MCR-08-0578

β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells. / Li, Timothy T.; Alemayehu, Mistre; Aziziyeh, Adel I.; Pape, Cynthia; Pampillo, Macarena; Postovit, Lynne Marie; Mills, Gordon; Babwah, Andy V.; Bhattacharya, Moshmi.

In: Molecular Cancer Research, Vol. 7, No. 7, 01.07.2009, p. 1064-1077.

Research output: Contribution to journalArticle

Li, TT, Alemayehu, M, Aziziyeh, AI, Pape, C, Pampillo, M, Postovit, LM, Mills, G, Babwah, AV & Bhattacharya, M 2009, 'β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells', Molecular Cancer Research, vol. 7, no. 7, pp. 1064-1077. https://doi.org/10.1158/1541-7786.MCR-08-0578
Li, Timothy T. ; Alemayehu, Mistre ; Aziziyeh, Adel I. ; Pape, Cynthia ; Pampillo, Macarena ; Postovit, Lynne Marie ; Mills, Gordon ; Babwah, Andy V. ; Bhattacharya, Moshmi. / β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells. In: Molecular Cancer Research. 2009 ; Vol. 7, No. 7. pp. 1064-1077.
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abstract = "The lipid mediator lysophosphatidic acid (LPA) plays a role in cancer progression and signals via specific G protein-coupled receptors, LPA1-3.LPA has been shown to enhance the metastasis of breast carcinoma cells to bone. However, the mechanisms by which LPA receptors regulate breast cancer cell migration and invasion remain unclear. Breast cancer cell proliferation has been shown to be stimulated by Ral GTPases, amember of the Ras superfamily. Ral activity can be regulated by the multifunctional protein {\^a}-arrestin.We now show that HS578T and MDA-MB-231 breast cancer cells and MDA-MB-435 melanoma cells have higher expression of {\^a}-arrestin 1 mRNA compared with the nontumorigenic mammary MCF-10A cells.Moreover, we found that the mRNA levels of LPA1, LPA2, {\^a}-arrestin 2, and Ral GTPases are elevated in the advanced stages of breast cancer.LPA stimulates the migration and invasion of MDA-MB-231 cells, but not of MCF-10A cells, and this is mediated by pertussis toxin-sensitive G proteins and LPA1. However, ectopic expression of LPA1 in MCF-10A cells caused these cells to acquire an invasive phenotype.Ge ne knockdown of either {\^a}-arrestin or Ral proteins significantly impaired LPA-stimulated migration and invasion.Th us, our data show a novel role for {\^a}-arrestin/Ral signaling in mediating LPA-induced breast cancer cell migration and invasion, two important processes in metastasis.",
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