TY - JOUR
T1 - β-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells
AU - Li, Timothy T.
AU - Alemayehu, Mistre
AU - Aziziyeh, Adel I.
AU - Pape, Cynthia
AU - Pampillo, Macarena
AU - Postovit, Lynne Marie
AU - Mills, Gordon
AU - Babwah, Andy V.
AU - Bhattacharya, Moshmi
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
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U2 - 10.1158/1541-7786.MCR-08-0578
DO - 10.1158/1541-7786.MCR-08-0578
M3 - Article
C2 - 19609003
AN - SCOPUS:67651151233
SN - 1541-7786
VL - 7
SP - 1064
EP - 1077
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 7
ER -