Molecular causes of elevated phosphoethanolamine in breast and pancreatic cancer cells
Shah, Tariq; Krishnamachary, Balaji; Wildes, Flonne; Wijnen, Jannie P.; Glunde, Kristine; Bhujwalla, Zaver M.
(2018) NMR in Biomedicine, volume 31, issue 8
(Article)
Abstract
Elevated phosphoethanolamine (PE) is frequently observed in MRS studies of human cancers and xenografts. The role of PE in cell survival and the molecular causes underlying this increase are, however, relatively underexplored. In this study, we investigated the roles of ethanolamine kinases (Etnk-1 and 2) and choline kinases (Chk-α and
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β) in contributing to increased PE in human breast and pancreatic cancer cells. We investigated the effect of silencing Etnk-1 and Etnk-2 on cell viability as a potential therapeutic strategy. Both breast and pancreatic cancer cells showed higher PE compared with their nonmalignant counterparts. We identified Etnk-1 as a major cause of the elevated PE levels in these cancer cells, with little or no contribution from Chk-α, Chk-β, or Etnk-2. The increase of PE observed in pancreatic cancer cells in culture was replicated in the corresponding tumor xenografts. Downregulation of Etnk-1 with siRNA resulted in cell cytotoxicity that correlated with PE levels in breast and pancreatic cancer cells. Etnk-1 may provide a potential therapeutic target in breast and pancreatic cancers.
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Keywords: breast cancer, choline kinase, ethanolamine kinase, metabolism, MRS, pancreatic cancer, Ethanolamines/metabolism, Glycerylphosphorylcholine/metabolism, Phosphorylcholine/metabolism, Epithelial Cells/metabolism, Magnetic Resonance Spectroscopy, Cell Survival, Down-Regulation, Humans, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms/genetics, RNA, Messenger/genetics, RNA, Small Interfering/metabolism, Xenograft Model Antitumor Assays, Animals, Phosphorus/chemistry, Cell Line, Tumor, Female, Breast Neoplasms/genetics, Molecular Medicine, Radiology Nuclear Medicine and imaging, Spectroscopy, Journal Article, Research Support, N.I.H., Extramural
ISSN: 0952-3480
Publisher: John Wiley and Sons Ltd
Note: Funding Information: This work was supported by NIH R35CA209960, R01CA82337 and NIH P30CA06973. Publisher Copyright: Copyright © 2018 John Wiley & Sons, Ltd. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
(Peer reviewed)