Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.
نویسندگان
چکیده
Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589-601. ©2017 AACR.
منابع مشابه
Highlight report: The EDI3-GPAM axis in tumor cell migration
Recently, the glycerophosphodiesterase EDI3 (GPCPD1) has been shown to represent a key factor of choline metabolism that mediates tumor cell migration, adhesion and spreading (Stewart et al., 2012; Lesjak et al., 2014). EDI3 cleaves glycerophosphocholine to choline and glycerol-3-phosphate (Marchan et al., 2012). Choline is further metabolized by choline kinase alpha (CHKA) that generates phosp...
متن کاملOvarian Small Cell Carcinoma: A Rare Case Report and Review of Literature
Ovarian small cell carcinoma is a rare and highly malignant tumor with poor prognosis. It usually presents in younger females with features of hypercalcemia. The exact histogenesis of the tumor is unclear and it may present as an undifferentiated tumor. In such cases, immunohistochemistry (IHC) plays an important role to confirm the diagnosis. Limited treatment options are available and mainly ...
متن کاملAnionic glycolipids related to glucuronosyldiacylglycerol inhibit protein kinase Akt.
New glucuronosyldiacylglycerol (GlcADG) analogues based on a 2-O-β-D-glucopyranosyl-sn-glycerol scaffold and carrying one or two acyl chains of different lengths have been synthesized as phosphatidylinositol 3-phosphate (PI3P) mimics targeting the protein kinase Akt. The Akt inhibitory effect of the prepared compounds was assayed using an in vitro kinase assay. The antiproliferative activity of...
متن کاملGlycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene and Promotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 Cell Line
The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics appr...
متن کاملCharacterization of Escherichia coli cells deficient in 1-acyl-sn-glycerol-3- phosphate acyltransferase activity.
A mutant of Escherichia coli K-12 defective in 1-acyl-sn-glycerol-3-phosphate acyltransferase has been isolated. At the permissive temperature for growth, 30 degrees C, 20% of the total cellular glycerophospholipids is 1-acyl-sn-glycerol-3-phosphate, as identified by mass spectral analysis and proton NMR. This percentage of 1-acyl-sn-glycerol-3-phosphate rises to about 30% when the temperature ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 77 17 شماره
صفحات -
تاریخ انتشار 2017