Basic—Alimentary TractMAGI-3 Competes With NHERF-2 to Negatively Regulate LPA2 Receptor Signaling in Colon Cancer Cells
Section snippets
Cells
HCT116 and SW480 human colon cancer cells were grown and transfected as previously described.12 pcDNA3.1 harboring MAGI-3 or NHERF-2 was described previously.6, 12 Knockdown of MAGI-3, NHERF-2, or LPA2 was performed as previously described.11 Stable expression of LPA2 was achieved by using retroviral pLPCX harboring vesicular stomatitis virus glycoprotein-tagged LPA2, pLPCX/VSVG-LPA2, or pLPCX (Roche, Indianapolis, IN). Unless otherwise stated, cells were serum-starved for 24 hours followed by
NHERF-2 and MAGI-3 Reciprocally Regulate LPA2-Mediated Cellular Functions
To determine the role of MAGI-3 and NHERF-2, we used human colon cancer HCT116 cells, which express NHERF-2 and MAGI-3. We have shown previously that LPA2 is the major LPA receptor in Caco-2 and other colon cancer cells.6 Consequently, silencing of LPA2 expression abrogated LPA-induced migration of HCT116 cells, whereas overexpression of LPA2 enhanced cell migration (Figure 1A and B; Supplementary Figure 1A and B). Consistent with previous reports that NHERF-2 enhances LPA2-evoked cell
Discussion
The role of LPA signaling in the progression of cancer is an active area of study. Since the initial demonstration of the effect of LPA on cell proliferation, the identification of LPA as the ovarian-cancer activating factor in malignant ascites together with the finding of increased levels of LPA in ovarian and other gynecologic cancers have heightened the relevance of LPA to cancer.22, 23, 24 The recent report that free fatty acid generation in cancer cells produces oncogenic lipids, such as
Acknowledgments
The authors thank Dr Pann-Ghill Suh for phospholipase C–β clones; and the authors acknowledge the Emory Digestive Disease Research Development Center (supported by grant DK064399) for providing HCT116 and SW480 cells.
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by grants from the National Institutes of Health (R01DK071597 and R01DK071597-03S1 to C.C.Y. and R01NS055179 to R.A.H.).