Evidence map›Paper›PMID 24958816›Full record

ArticleMolecular pharmacology2014

Gα13/PDZ-RhoGEF/RhoA signaling is essential for gastrin-releasing peptide receptor-mediated colon cancer cell migration.

Maulik Patel, Takeharu Kawano, Nobuchika Suzuki, Takao Hamakubo, Andrei V Karginov, Tohru Kozasa

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.6field-weighted citation impact, top 5% 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, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Advances of radiolabeled GRPR ligands for PET/CT imaging of cancers.Cancer imaging : the official publication of the International Cancer Imaging Society · 2024
    Review
  4. GαFrontiers in cell and developmental biology · 2022
    Review
  5. GPCRs thatSmall GTPases · 2022
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Lifetime of muscarinic receptor-G-protein complexes determines coupling efficiency and G-protein subtype selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice.American journal of physiology. Lung cellular and molecular physiology · 2015
    Article
  17. Review
  18. Article
  19. RhoA/mDia-1/profilin-1 signaling targets microvascular endothelial dysfunction in diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2015
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Maulik PatelDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.).
Takeharu KawanoDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.).
Nobuchika SuzukiDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.).
Takao HamakuboDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.).
Andrei V KarginovDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.).
Tohru KozasaDepartment of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, Illinois (M.P., A.V.K., T.Ko.); Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia (T. Ka.); and Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan (N.S., T.H., T.Ko.). karginov@uic.edu kozasa@lsbm.org.
University of Illinois Chicago · USVirginia Commonwealth University · US

Funding

Regulation of Rho family GTPases by heterotrimeric G proteinsR01GM061454 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KOZASA, TOHRU, KREUTZ, BARRY S. · 1999 to 2014
$3.3M
New methods for activation of kinases and kinase circuits in living cells.R21CA159179 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2012 to 2013
$371k
NCI NIH HHS R21CA159179NHLBI NIH HHS HL007829NIGMS NIH HHS GM61454
6 · The paper itself

Abstract

Gastrin-releasing peptide receptor (GRPR) is ectopically expressed in over 60% of colon cancers. GRPR expression has been correlated with increased colon cancer cell migration. However, the signaling pathway by which GRPR activation leads to increased cancer cell migration is not well understood. We set out to molecularly dissect the GRPR signaling pathways that control colon cancer cell migration through regulation of small GTPase RhoA. Our results show that GRP stimulation activates RhoA predominantly through G13 heterotrimeric G-protein signaling. We also demonstrate that postsynaptic density 95/disk-large/ZO-1 (PDZ)-RhoGEF (PRG), a member of regulator of G-protein signaling (RGS)-homology domain (RH) containing guanine nucleotide exchange factors (RH-RhoGEFs), is the predominant activator of RhoA downstream of GRPR. We found that PRG is required for GRP-stimulated colon cancer cell migration, through activation of RhoA-Rho-associated kinase (ROCK) signaling axis. In addition, PRG-RhoA-ROCK pathway also contributes to cyclo-oxygenase isoform 2 (Cox-2) expression. Increased Cox-2 expression is correlated with increased production of prostaglandin-E2 (PGE2), and Cox-2-PGE2 signaling contributes to total GRPR-mediated cancer cell migration. Our analysis reveals that PRG is overexpressed in colon cancer cell lines. Overall, our results have uncovered a key mechanism for GRPR-regulated colon cancer cell migration through the Gα13-PRG-RhoA-ROCK pathway.

Indexed as

Caco-2 CellsCell MovementColonic NeoplasmsCyclooxygenase 2DinoprostoneDisks Large Homolog 4 ProteinGTP-Binding Protein alpha Subunits, G12-G13HT29 CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsProtein Structure, TertiaryReceptors, BombesinrhoA GTP-Binding Proteinrho-Associated KinasesRho Guanine Nucleotide Exchange FactorsCyclooxygenase 2DinoprostoneDisks Large Homolog 4 ProteinDLG4 protein, humanGTP-Binding Protein alpha Subunits, G12-G13Intracellular Signaling Peptides and ProteinsMembrane ProteinsReceptors, BombesinrhoA GTP-Binding ProteinRHOA protein, humanrho-Associated KinasesRho Guanine Nucleotide Exchange FactorsTJP1 protein, humanZonula Occludens-1 Protein

Identifiers

PMID24958816
PMCPMC4576495
OpenAlexW2096379425

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.