Evidence map›Paper›PMID 21134377›Full record

ArticleGastroenterology2011

MAGI-3 competes with NHERF-2 to negatively regulate LPA2 receptor signaling in colon cancer cells.

Sei-Jung Lee, Stefanie L Ritter, Huanchun Zhang, Hyunsuk Shim, Randy A Hall, C Chris Yun

Abstract read
In one paragraph

Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. World journal of gastrointestinal oncology · 2022
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. The Journal of biological chemistry · 2020
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018
    Article
  18. Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  19. Deletion of Na+/H+ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24.American journal of physiology. Gastrointestinal and liver physiology · 2016
    Article
  20. 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

6 authors at 1 institution in 1 country.

Sei-Jung LeeDivision of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Stefanie L Ritter
Huanchun Zhang
Hyunsuk Shim
Randy A Hall
C Chris Yun
Emory University · US

Funding

Emory Epithelial Pathobiology Research Development CenterR24DK064399 · NIDDK · EMORY UNIVERSITY · PI PARKOS, CHARLES A · 2003 to 2012
$5.3M
LPA Receptor Signaling in Colonic EpitheliaR01DK071597 · NIDDK · EMORY UNIVERSITY · PI YUN, CHANGHYON CHRIS · 2007 to 2015
$3.0M
PDZ scaffold regulation of astrocytic glutamate receptors and transportersR01NS055179 · NINDS · EMORY UNIVERSITY · PI HALL, RANDY A. · 2008 to 2012
$1.5M
NIDDK NIH HHS R01 DK071597NIDDK NIH HHS R01DK071597NIDDK NIH HHS R01DK071597-03S1NIDDK NIH HHS R24 DK064399NINDS NIH HHS R01 NS055179NINDS NIH HHS R01NS055179
6 · The paper itself

Abstract

BACKGROUND &

aimsLysophosphatidic acid (LPA) is a potent inducer of colon cancer and LPA receptor type 2 (LPA(2)) is overexpressed in colon tumors. LPA(2) interacts with membrane-associated guanylate kinase with inverted orientation-3 (MAGI-3) and the Na+/H+ exchanger regulatory factor 2 (NHERF-2), but the biological effects of these interactions are unknown. We investigated the roles of MAGI-3 and NHERF-2 in LPA(2)-mediated signaling in human colon cancer cells.

methodsWe overexpressed or knocked down MAGI-3 in HCT116 and SW480 cells. The effects of MAGI-3 and NHERF-2 in LPA-induced cell migration, invasion, inositol phosphate generation, and nuclear factor-κB activation were determined. Expression of MAGI-3 and NHERF-2 in human colon tumor tissues was analyzed using tissue microarray analysis.

resultsNHERF-2 promoted migration and invasion of colon cancer cells, whereas MAGI-3 inhibited these processes. MAGI-3 competed with NHERF-2 for binding to LPA(2) and phospholipase C-β3. However, NHERF-2 and MAGI-3 reciprocally regulated LPA(2)-induced phospholipase C activity. MAGI-3 increased the interaction of LPA(2) with Gα(12), whereas NHERF-2 preferentially promoted interaction between LPA(2) and Gα(q). MAGI-3 decreased the tumorigenic capacity of LPA(2) by attenuating the activities of nuclear factor-κB and c-Jun N-terminal kinase. MAGI-3 and NHERF-2 were expressed differentially in colon adenocarcinomas, consistent with their opposing effects.

conclusionsLPA(2) is dynamically regulated by 2 distinct PDZ proteins via modulation of G-protein coupling and receptor signaling. MAGI-3 is a negative regulator of LPA(2) signaling.

Indexed as

Signal TransductionAdenocarcinomaAdenomatous Polyposis ColiAnimalsCell MovementColonic NeoplasmsDisease Models, AnimalGenes, APCGTP-Binding Protein alpha Subunits, G12-G13GTP-Binding Protein alpha Subunits, Gq-G11HCT116 CellsHumansInositol PhosphatesJNK Mitogen-Activated Protein KinasesLysophospholipidsMembrane ProteinsGTP-Binding Protein alpha Subunits, G12-G13GTP-Binding Protein alpha Subunits, Gq-G11Inositol PhosphatesJNK Mitogen-Activated Protein Kinaseslysophosphatidic acidLysophospholipidsMAGI3 protein, humanMembrane ProteinsNF-kappa BPhospholipase C betaPhosphoproteinsPLCB3 protein, humanReceptors, Lysophosphatidic Acidsodium-hydrogen exchanger regulatory factorSodium-Hydrogen Exchangers

Identifiers

PMID21134377
PMCPMC3057353
OpenAlexW2151134851

What OpenQuestion holds

Textmetadata
LicenceTDM
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.