Evidence map›Paper›PMID 26765257›Full record

ArticlePLoS genetics2016

A Sensitized Screen for Genes Promoting Invadopodia Function In Vivo: CDC-42 and Rab GDI-1 Direct Distinct Aspects of Invadopodia Formation.

Lauren L Lohmer, Matthew R Clay, Kaleb M Naegeli, Qiuyi Chi, Joshua W Ziel, Elliott J Hagedorn, Jieun E Park, Ranjay Jayadev, David R Sherwood

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.9field-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

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  11. Pioneer Axons Utilize aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  12. Review
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  15. Article
  16. Article
  17. ACancer cell international · 2019
    Article
  18. Forces drive basement membrane invasion inProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Review
  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

9 authors at 2 institutions in 1 country.

Lauren L LohmerDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Matthew R ClayDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Kaleb M NaegeliDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Qiuyi ChiDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Joshua W ZielDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Elliott J HagedornStem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
Jieun E ParkDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Ranjay JayadevDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
David R SherwoodDepartment of Biology, Duke University, Durham, North Carolina, United States of America.
Duke University · USHarvard University · US

Funding

ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
Training Program in Developmental & Stem Cell BiologyT32HD040372 · NICHD · DUKE UNIVERSITY · PI Terry H Lechler · 2001 to 2026
$8.9M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Genetic Analysis of Cell Invasion through Basement MembranesR01GM079320 · NIGMS · DUKE UNIVERSITY · PI SHERWOOD, DAVID R · 2007 to 2015
$2.8M
Understanding How Invadosomes Breach Basement Membrane In VivoR01GM100083 · NIGMS · DUKE UNIVERSITY · PI SHERWOOD, DAVID R · 2012 to 2015
$1.1M
NICHD NIH HHS T32 HD040372NIGMS NIH HHS GM079329NIGMS NIH HHS GM100083NIGMS NIH HHS R01 GM079320NIGMS NIH HHS R01 GM100083NIGMS NIH HHS T32 GM007184NIH HHS P40 OD010440
6 · The paper itself

Abstract

Invadopodia are specialized membrane protrusions composed of F-actin, actin regulators, signaling proteins, and a dynamically trafficked invadopodial membrane that drive cell invasion through basement membrane (BM) barriers in development and cancer. Due to the challenges of studying invasion in vivo, mechanisms controlling invadopodia formation in their native environments remain poorly understood. We performed a sensitized genome-wide RNAi screen and identified 13 potential regulators of invadopodia during anchor cell (AC) invasion into the vulval epithelium in C. elegans. Confirming the specificity of this screen, we identified the Rho GTPase cdc-42, which mediates invadopodia formation in many cancer cell lines. Using live-cell imaging, we show that CDC-42 localizes to the AC-BM interface and is activated by an unidentified vulval signal(s) that induces invasion. CDC-42 is required for the invasive membrane localization of WSP-1 (N-WASP), a CDC-42 effector that promotes polymerization of F-actin. Loss of CDC-42 or WSP-1 resulted in fewer invadopodia and delayed BM breaching. We also characterized a novel invadopodia regulator, gdi-1 (Rab GDP dissociation inhibitor), which mediates membrane trafficking. We show that GDI-1 functions in the AC to promote invadopodia formation. In the absence of GDI-1, the specialized invadopodial membrane was no longer trafficked normally to the invasive membrane, and instead was distributed to plasma membrane throughout the cell. Surprisingly, the pro-invasive signal(s) from the vulval cells also controls GDI-1 activity and invadopodial membrane trafficking. These studies represent the first in vivo screen for genes regulating invadopodia and demonstrate that invadopodia formation requires the integration of distinct cellular processes that are coordinated by an extracellular cue.

Indexed as

AnimalsBasement MembraneCaenorhabditis elegansCaenorhabditis elegans ProteinsCell Cycle ProteinsDisease Models, AnimalExtracellular MatrixGene Expression Regulation, DevelopmentalGTP-Binding ProteinsGuanine Nucleotide Dissociation InhibitorsHumansNeoplasmsPodosomesSignal TransductionCaenorhabditis elegans Proteinscdc-42 protein, C elegansCell Cycle ProteinsGDP dissociation inhibitor 1GTP-Binding ProteinsGuanine Nucleotide Dissociation Inhibitors

Identifiers

PMID26765257
PMCPMC4713207
OpenAlexW2238732613

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.