Evidence map›Paper›PMID 24659799›Full record

ArticleJournal of cell science2014

Rab5 is required in metastatic cancer cells for Caveolin-1-enhanced Rac1 activation, migration and invasion.

Jorge Díaz, Pablo Mendoza, Rina Ortiz, Natalia Díaz, Lisette Leyton, Dwayne Stupack, Andrew F G Quest, Vicente A Torres

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing 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

61 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. The IPBiochimica et biophysica acta. Molecular basis of disease · 2025
    Article
  6. Article
  7. Uptake ofInternational journal of molecular sciences · 2023
    Article
  8. Article
  9. Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. lncRNA HITT inhibits metastasis by attenuating Rab5-mediated endocytosis in lung adenocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  15. Caveolin1: its roles in normal and cancer stem cells.Journal of cancer research and clinical oncology · 2021
    Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 2 countries.

Jorge DíazInstitute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone 943, Santiago, Chile Center for Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
Pablo MendozaInstitute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone 943, Santiago, Chile.
Rina OrtizCenter for Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
Natalia DíazCenter for Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
Lisette LeytonAdvanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Program of Cell and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
Dwayne StupackMoores UCSD Cancer Center, University of California, La Jolla, CA 92093, USA.
Andrew F G QuestCenter for Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile Program of Cell and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile aquest@med.uchile.cl vatorres@med.uchile.cl.
Vicente A TorresInstitute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone 943, Santiago, Chile Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile aquest@med.uchile.cl vatorres@med.uchile.cl.
University of Chile · CLAdvanced Center for Chronic Diseases · CLUniversity of California, San Diego · US

Funding

Integrins and Caspase 8 in Tumor ProgressionR01CA107263 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI STUPACK, DWAYNE G. · 2005 to 2014
$3.1M
NCI NIH HHS R01 CA107263
6 · The paper itself

Abstract

Rab5 is a small GTPase that regulates early endosome trafficking and other cellular processes, including cell adhesion and migration. Specifically, Rab5 promotes Rac1 activation and cancer cell migration, but little is known about the upstream regulators of Rab5. We have previously shown that the scaffolding protein Caveolin-1 (CAV1) promotes Rac1 activation and migration of cancer cells. Here, we hypothesized that CAV1 stimulates Rab5 activation, leading to increased Rac1 activity and cell migration. Expression of CAV1 in B16-F10 mouse melanoma and HT-29(US) human colon adenocarcinoma cells increased the GTP loading of Rab5, whereas shRNA-mediated targeting of endogenous CAV1 in MDA-MB-231 breast cancer cells decreased Rab5-GTP levels. Accordingly, shRNA-mediated downregulation of Rab5 decreased CAV1-mediated Rac1 activation, cell migration and invasion in B16-F10 and HT-29(US) cells. Expression of CAV1 was accompanied by increased recruitment of Tiam1, a Rac1 guanine nucleotide exchange factor (GEF), to Rab5-positive early endosomes. Using the inhibitor NSC23766, Tiam1 was shown to be required for Rac1 activation and cell migration induced by CAV1 and Rab5. Mechanistically, we provide evidence implicating p85α (also known as PIK3R1), a Rab5 GTPase-activating protein (GAP), in CAV1-dependent effects, by showing that CAV1 recruits p85α, precluding p85α-mediated Rab5 inactivation and increasing cell migration. In summary, these studies identify a novel CAV1-Rab5-Rac1 signaling axis, whereby CAV1 prevents Rab5 inactivation, leading to increased Rac1 activity and enhanced tumor cell migration and invasion.

Indexed as

AminoquinolinesAnimalsCaveolin 1Cell MovementClass Ia Phosphatidylinositol 3-KinaseDNA-Binding ProteinsGuanine Nucleotide Exchange FactorsHT29 CellsHumansMelanoma, ExperimentalMiceNeoplasm InvasivenessNeoplasm MetastasisPhosphatidylinositol 3-KinasesPyrimidinesrab5 GTP-Binding ProteinsAminoquinolinesCaveolin 1Class Ia Phosphatidylinositol 3-KinaseDNA-Binding ProteinsGuanine Nucleotide Exchange FactorsNSC 23766Phosphatidylinositol 3-KinasesPIK3R1 protein, humanPyrimidinesrab5 GTP-Binding Proteinsrac1 GTP-Binding ProteinRNA, Small InterferingSLC2A4RG protein, humanTIAM1 protein, humanT-Lymphoma Invasion and Metastasis-inducing Protein 1Transcription FactorsCaveolin-1Metastatic cell migrationp85αRab5Rac1Small GTPases

Identifiers

PMID24659799
PMCPMC4074264
OpenAlexW2142793416

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.