Premium
Lysophosphatidic acid in ascites from ovarian cancer patients selectively activates Akt1 to induce cell migration
Author(s) -
Kim Eun Kyoung,
Yun Sung Ji,
Do Kee Hun,
Kim Min Sung,
Kim Jae Ho,
Kim Chi Dae,
Bae Sun Sik
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.580
Subject(s) - lysophosphatidic acid , cell migration , akt2 , akt1 , ovarian cancer , cancer research , cell , pi3k/akt/mtor pathway , chemistry , cell growth , ly294002 , microbiology and biotechnology , biology , medicine , signal transduction , receptor , cancer , biochemistry
Lysophosphatidic acid (LPA) is major serum lysophospholipid that induces migration in many cell types including ovarian cancer cells. Here we reported that ascites from ovarian cancer patients (AOCP) induced cell migration in a dose‐dependent manner but not by ascites from liver cirrhosis patients (ALCP). AOCP‐induced cell migration was completely blocked by pretreatment of PI3K inhibitor (LY294002). In addition, cells lacking Akt1 and Akt2 (DKO) showed impairment of AOCP‐induced cell migration. Interestingly, add‐back of Akt1 into DKO cells restored AOCP‐induced cell migration but not by Akt2. In correlation with this, AOCP preferentially induced the phosphorylation of Akt1 rather than Akt2. AOCP‐induced cell migration was also completely blocked by LPA receptor antagonist (Ki16425). Likewise, LPA‐induced cell migration was completely blocked by pretreatment of PI3K inhibitor (LY294002) and showed defects in cells lacking Akt1 such as DKO cells. Re‐introduction of Akt1 into DKO cells restored LPA‐induced cell migration. LPA also preferentially activated Akt1 rather than Akt2. Finally, we showed that silencing of P‐Rex1 by siRNA completely abolished LPA‐dependent cell migration. Given these results, we suggest that LPA might be major component of ascites from ovarian cancer patients that induces cell migration through the preferential activation of Akt1. P‐Rex1 might play critical role in LPA‐induced cell migration through specific molecular complex formation with Akt1.