Journal
JOURNAL OF CELL SCIENCE
Volume 116, Issue 18, Pages 3835-3846Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.00679
Keywords
LPA; migration; Ras; Rho; ERK; pancreatic carcinoma
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Lysophosphatidic acid (LPA) is a serum-borne phospholipid with hormone and growth factor-like properties. LPA has been shown to modulate tumor cell invasion and malignant cell growth. Here, we report that two human pancreatic carcinoma cell lines, PANC-1 and BxPC-3, express functionally active LPA receptors coupled to pertussis toxin-sensitive G(i/o)-proteins. In contrast to other cell types, LPA does not act as a mitogen, but is an efficacious stimulator of cell migration of these tumor cells. LPA-induced chemotaxis is markedly dependent on activation of PTX-sensitive heterotrimeric G-proteins, on activation of the small GTPases Ras, Rac and RhoA, and on GTPase-dependent activation of ERK. LPA-induced ERK activation results in a transient translocation of the phosphorylated ERK to newly forming focal contact sites at the leading edge of the migrating cells. Inhibition of ERK activation and its subsequent translocation impaired LPA-induced chemotaxis and LPA-induced actin reorganization. Thus, pancreatic tumor cell migration in response to LPA is essentially controlled by activation of a G(i/o)-ERK pathway and requires the LPA-induced activation of Ras, Rac1 and RhoA.
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