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Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma

Rosemarie Marchan1, Bettina Büttner2, Jörg Lambert3

  • 1Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany. marchan@ifado.de.

Cancer Research
|June 28, 2017
PubMed

Insights

Glycerol-3-phosphate acyltransferase (GPAM) promotes ovarian cancer cell migration and tumor growth by influencing lysophosphatidic acid (LPA) levels. Targeting GPAM may offer a new therapeutic strategy for ovarian cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Glycerophosphodiesterase EDI3 (GPCPD1) is implicated in cell migration, but its downstream signaling pathways are unclear.
  • GPAM and CHKA are enzymes that metabolize EDI3 products, suggesting potential roles in cell migration.
  • Understanding these pathways is crucial for identifying therapeutic targets in cancer.

Purpose of the Study:

  • To investigate the downstream signaling pathways of GPCPD1, specifically focusing on GPAM and CHKA.
  • To determine the role of GPAM and CHKA in cell migration and their link to GPCPD1.
  • To explore the therapeutic potential of targeting GPAM in ovarian cancer.

Main Methods:

  • Enzyme activity assays to measure GPAM and CHKA function.
  • Cell migration assays to assess the impact of GPAM and CHKA manipulation.
  • Analysis of GPAM expression in human cancer types and its correlation with survival.
  • Tumor xenograft studies in mice to evaluate the effect of GPAM silencing on tumor growth.

Main Results:

  • GPAM, but not CHKA, significantly influenced cell migration, primarily through the signaling lipid lysophosphatidic acid (LPA).
  • High GPAM expression correlated with reduced overall survival in ovarian cancer patients.
  • Silencing GPAM in ovarian cancer cells decreased cell migration and inhibited tumor xenograft growth.
  • GPAM's role in promoting cell migration and tumor growth was linked to its influence on intracellular LPA levels.

Conclusions:

  • GPAM plays a critical role in promoting cell migration and tumor growth by regulating intracellular LPA levels.
  • GPAM is a potential therapeutic target for ovarian cancer, as its inhibition reduces tumor progression.
  • The study elucidates a novel mechanism linking GPAM, LPA signaling, and cancer cell behavior.

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