Evidence map›Paper›PMID 24556997›Full record

ArticleCancer biology & therapy2014

Phospholipase D1 and choline kinase-α are interactive targets in breast cancer.

Mayur Gadiya, Noriko Mori, Maria D Cao, Yelena Mironchik, Samata Kakkad, Ingrid S Gribbestad, Kristine Glunde, Balaji Krishnamachary, Zaver M Bhujwalla

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Phospholipase D and Choline Metabolism.Handbook of experimental pharmacology · 2020
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Choline metabolism-based molecular diagnosis of cancer: an update.Expert review of molecular diagnostics · 2015
    Review
  18. Article
  19. Review
  20. Sizing up surfactant synthesis.Cell metabolism · 2014
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Mayur GadiyaDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Noriko MoriDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Maria D CaoDepartment of Circulation and Medical Imaging; Norwegian University of Science and Technology (NTNU); Trondheim, Norway.
Yelena MironchikDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Samata KakkadDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Ingrid S GribbestadDepartment of Circulation and Medical Imaging; Norwegian University of Science and Technology (NTNU); Trondheim, Norway.
Kristine GlundeDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Balaji KrishnamacharyDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Zaver M BhujwallaDivision of Cancer Imaging Research; The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center; Russell H. Morgan Department of Radiology and Radiological Science; The Johns Hopkins University School of Medicine; Baltimore, MD USA; Sidney Kimmel Comprehensive Cancer Center; The Johns Hopkins University School of Medicine; Baltimore, MD USA.
Johns Hopkins Medicine · USImaging Center · USNorwegian University of Science and Technology · NOUniversity of Baltimore · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Theranostic Imaging of Metastatic Prostate CancerP50CA103175 · NCI · JOHNS HOPKINS UNIVERSITY · PI BARKER, PETER B · 2003 to 2015
$17.9M
HOSTILE ENVIRONMENTS PROMOTE INVASION AND METATASISR01CA082337 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 1999 to 2024
$5.1M
FUNTIONAL IMAGING OF THE METASTATIC PHENOTYPER01CA073850 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 1997 to 2014
$3.5M
Imaging Hypoxia and Cancer Stem CellsR01CA136576 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 2009 to 2017
$2.4M
Image-guided Prodrug and siRNA Targeting of CancerR01CA138515 · NCI · JOHNS HOPKINS UNIVERSITY · PI BHUJWALLA, ZAVER M. · 2009 to 2013
$1.7M
Imaging hypoxia-driven signaling pathways in the breast tumor microenvironmentR01CA134695 · NCI · JOHNS HOPKINS UNIVERSITY · PI GLUNDE, KRISTINE · 2008 to 2012
$1.5M
NCI NIH HHS P30 CA006973NCI NIH HHS P30CA006973NCI NIH HHS P50 CA103175NCI NIH HHS P50CA103175NCI NIH HHS R01 CA073850NCI NIH HHS R01 CA082337NCI NIH HHS R01 CA134695NCI NIH HHS R01 CA136576NCI NIH HHS R01CA136576NCI NIH HHS R01 CA138515NCI NIH HHS R01CA138515NCI NIH HHS R01CA73850NCI NIH HHS R01CA82337
6 · The paper itself

Abstract

A consistent metabolic hallmark observed in multiple cancers is the increase of cellular phosphocholine (PC) and total choline-containing compounds (tCho), which is closely related to malignant transformation, invasion, and metastasis. Enzymes in choline phospholipid metabolism present attractive targets to exploit for treatment, but require a clear understanding of the mechanisms underlying the altered choline phospholipid metabolism observed in cancer. Choline kinase-α (Chk-α) is an enzyme in the Kennedy pathway that phosphorylates free choline (Cho) to PC, and its upregulation in several cancers is a major contributor to increased PC levels. Similarly, increased expression and activity of phospholipase D1 (PLD1), which converts phosphatidylcholine (PtdCho) to phosphatidic acid (PA) and Cho, has been well documented in gastric, ovarian and breast cancer. Here we report a strong correlation between expression of Chk-α and PLD1 with breast cancer malignancy. Data from patient samples established an association between estrogen receptor (ER) status and Chk-α and PLD1 expression. In addition, these two enzymes were found to be interactive. Downregulation of Chk-α with siRNA increased PLD1 expression, and downregulation of PLD1 increased Chk-α expression. Simultaneous silencing of PLD1 and Chk-α in MDA-MB-231 cells increased apoptosis as detected by the TUNEL assay. These data provide new insights into choline phospholipid metabolism of breast cancer, and support multiple targeting of enzymes in choline phospholipid metabolism as a strategy for treatment.

Indexed as

AdultAgedApoptosisBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalCholine KinaseEstrogen Receptor alphaFemaleHumansMiddle AgedNeoplasm StagingPhosphatidylcholinesPhospholipase DRNA, MessengerCHKA protein, humanCholine KinaseESR1 protein, humanessential 303 forteEstrogen Receptor alphaPhosphatidylcholinesPhospholipase Dphospholipase D1RNA, MessengerRNA, Small Interferingbreast cancercholine kinase-alphamagnetic resonance spectroscopyphospholipase D1RNA interference

Identifiers

PMID24556997
PMCPMC4026082
OpenAlexW2063052612

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.