Evidence map›Paper›PMID 27813479›Full record

ArticleeLife2016

AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin.

Nicolas Aznar, Arjun Patel, Cristina C Rohena, Ying Dunkel, Linda P Joosen, Vanessa Taupin, Irina Kufareva, Marilyn G Farquhar, Pradipta Ghosh

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
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  10. Article
  11. Roles of AMP-Activated Protein Kinase (AMPK) in Mammalian Reproduction.Frontiers in cell and developmental biology · 2020
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Article
  19. Article
  20. Implications of AMPK in the Formation of Epithelial Tight Junctions.International journal of molecular sciences · 2018
    Review
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 1 institution in 1 country.

Nicolas AznarDepartment of Medicine, University of California, San Diego, San Diego, United States.
Arjun PatelDepartment of Medicine, University of California, San Diego, San Diego, United States.
Cristina C RohenaDepartment of Medicine, University of California, San Diego, San Diego, United States.
Ying DunkelDepartment of Medicine, University of California, San Diego, San Diego, United States.
Linda P JoosenDepartment of Medicine, University of California, San Diego, San Diego, United States.
Vanessa TaupinDepartment of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
Irina KufarevaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United States.
Marilyn G FarquharDepartment of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
Pradipta GhoshDepartment of Medicine, University of California, San Diego, San Diego, United States.ORCID 0000-0002-8917-3201
University of California San Diego · US

Funding

UCSD Cancer Center Training Program in Drug DevelopmentT32CA121938 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Bouvet, Dwayne G. Stupack · 2006 to 2026
$10.3M
Training Grant in GastroenterologyT32DK007202 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 1985 to 2022
$7.7M
Spatial Regulation of RGS and G Protein SignalingR01CA100768 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 2003 to 2019
$7.4M
Macromolecular DockingR01GM071872 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ABAGYAN, RUBEN · 2004 to 2017
$4.2M
The structural plasticity of chemokine and gp120 recognition by CCR5R01AI118985 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2015 to 2019
$2.7M
Chemokine interaction with CXCR4 and ACKR3: structure and activation mechanismsR01GM117424 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2016 to 2019
$2.2M
Modulation of G proteins by Growth FactorsR01CA160911 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 2013 to 2017
$1.8M
G Protein pathways as Novel Therapeutic and Diagnostic Targets in Liver FibrosisR01DK099226 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 2014 to 2016
$698k
NCI NIH HHS R01 CA100768NCI NIH HHS R01 CA160911NCI NIH HHS T32 CA121938NIAID NIH HHS R01 AI118985NIDDK NIH HHS R01 DK099226NIGMS NIH HHS R01 GM071872
6 · The paper itself

Abstract

Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor of metabolic stress stabilizes cell-cell junctions and maintains epithelial polarity; its activation by Metformin protects the epithelial barrier against stress and suppresses tumorigenesis. How AMPK protects the epithelium remains unknown. Here, we identify GIV/Girdin as a novel effector of AMPK, whose phosphorylation at a single site is both necessary and sufficient for strengthening mammalian epithelial tight junctions and preserving cell polarity and barrier function in the face of energetic stress. Expression of an oncogenic mutant of GIV (cataloged in TCGA) that cannot be phosphorylated by AMPK increased anchorage-independent growth of tumor cells and helped these cells to evade the tumor-suppressive action of Metformin. This work defines a fundamental homeostatic mechanism by which the AMPK-GIV axis reinforces cell junctions against stress-induced collapse and also provides mechanistic insight into the tumor-suppressive action of Metformin.

Indexed as

AMP-Activated Protein KinasesAnimalsCell LineHumansMicrofilament ProteinsPhosphorylationProtein Processing, Post-TranslationalTight JunctionsVesicular Transport ProteinsAMP-Activated Protein KinasesCCDC88A protein, humanMicrofilament ProteinsVesicular Transport Proteinscancer biologyccdc88a/GIRDINcell biologyColon cancerenergetic stressepithelial cell polarityhumanMetformin, AMPKtight junctions

Identifiers

PMID27813479
PMCPMC5119889
OpenAlexW2548257578

What OpenQuestion holds

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LicenceCC BY
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.