Evidence map›Paper›PMID 31304629›Full record

ArticleThe EMBO journal2019

ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas.

Fotine Libanje, Joel Raingeaud, Rui Luan, ZoéAp Thomas, Olivier Zajac, Joel Veiga, Laetitia Marisa, Julien Adam, Valerie Boige, David Malka and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Tumour invasion and dissemination.Biochemical Society transactions · 2022
    Review
  12. Review
  13. Article
  14. Article
  15. The mechanobiome: a goldmine for cancer therapeutics.American journal of physiology. Cell physiology · 2021
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Rock inhibition promotes NaScientific reports · 2020
    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

17 authors at 5 institutions in 3 countries.

Fotine LibanjeINSERM U-981, Gustave Roussy, Villejuif, France.
Joel RaingeaudINSERM U-981, Gustave Roussy, Villejuif, France.
Rui LuanINSERM U-981, Gustave Roussy, Villejuif, France.
ZoéAp ThomasINSERM U-981, Gustave Roussy, Villejuif, France.
Olivier ZajacINSERM U-981, Gustave Roussy, Villejuif, France.
Joel VeigaCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Laetitia MarisaProgramme "Cartes d'Identité des Tumeurs", Ligue Nationale Contre le Cancer, Paris, France.
Julien AdamPathology Department, Gustave Roussy, Villejuif, France.
Valerie BoigeDigestive Cancer Unit, Gustave Roussy, Villejuif, France.
David MalkaDigestive Cancer Unit, Gustave Roussy, Villejuif, France.
Diane GoéréDigestive Cancer Unit, Gustave Roussy, Villejuif, France.
Alan HallCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Jean-Yves SoazecPathology Department, Gustave Roussy, Villejuif, France.
Friedrich PrallInstitute of Pathology, University Medicine of Rostock, Rostock, Germany.
Maximiliano GelliDigestive Cancer Unit, Gustave Roussy, Villejuif, France.
Peggy DartiguesPathology Department, Gustave Roussy, Villejuif, France.
Fanny JaulinINSERM U-981, Gustave Roussy, Villejuif, France.ORCID 0000-0002-5110-1800
Institut Gustave Roussy · FRInserm · FRMemorial Sloan Kettering Cancer Center · USLa Ligue Contre le Cancer · FRUniversity of Rostock · DE

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
CNRS/INSERM ATIP-AVENIR ProgrammeFondation pour la recherche medicale FDT20160435539French government MESR PhD fellowshipGustave Roussy FoundationINCA PLBIO 2018-1-PLBIO-04-IGR-1LNCC comité IDF Subvention comité IDF 2019NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

The metastatic progression of cancer is a multi-step process initiated by the local invasion of the peritumoral stroma. To identify the mechanisms underlying colorectal carcinoma (CRC) invasion, we collected live human primary cancer specimens at the time of surgery and monitored them ex vivo. This revealed that conventional adenocarcinomas undergo collective invasion while retaining their epithelial glandular architecture with an inward apical pole delineating a luminal cavity. To identify the underlying mechanisms, we used microscopy-based assays on 3D organotypic cultures of Caco-2 cysts as a model system. We performed two siRNA screens targeting Rho-GTPases effectors and guanine nucleotide exchange factors. These screens revealed that ROCK2 inhibition triggers the initial leader/follower polarization of the CRC cell cohorts and induces collective invasion. We further identified FARP2 as the Rac1 GEF necessary for CRC collective invasion. However, FARP2 activation is not sufficient to trigger leader cell formation and the concomitant inhibition of Myosin-II is required to induce invasion downstream of ROCK2 inhibition. Our results contrast with ROCK pro-invasive function in other cancers, stressing that the molecular mechanism of metastatic spread likely depends on tumour types and invasion mode.

Indexed as

AdenocarcinomaAnimalsCaco-2 CellsCell Culture TechniquesCell Line, TumorColorectal NeoplasmsGene Expression Regulation, NeoplasticGuanine Nucleotide Exchange FactorsHumansMiceNeoplasm InvasivenessNeoplasm MetastasisOrganoidsrho-Associated KinasesRNA, Small InterferingFARP2 protein, humanGuanine Nucleotide Exchange Factorsrho-Associated KinasesRNA, Small InterferingROCK2 protein, humancollective migrationcolorectal carcinomaGTPasesinvasionleader cells

Identifiers

PMID31304629
PMCPMC6627234
OpenAlexW2949211191

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.