Evidence map›Paper›PMID 24920608›Full record

ArticleEMBO molecular medicine2014

A novel genome-wide in vivo screen for metastatic suppressors in human colon cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12.

Arnaud Duquet, Alice Melotti, Sonakshi Mishra, Monica Malerba, Chandan Seth, Arwen Conod, Ariel Ruiz i Altaba

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. TMED family genes and their roles in human diseases.International journal of medical sciences · 2023
    Pooled it
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  8. The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023
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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

7 authors at 1 institution in 1 country.

Arnaud DuquetDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Alice MelottiDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Sonakshi MishraDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Monica MalerbaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Chandan SethDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Arwen ConodDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Ariel Ruiz i AltabaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland Ariel.RuizAltaba@unige.ch.
University of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The progression of tumors to the metastatic state involves the loss of metastatic suppressor functions. Finding these, however, is difficult as in vitro assays do not fully predict metastatic behavior, and the majority of studies have used cloned cell lines, which do not reflect primary tumor heterogeneity. Here, we have designed a novel genome-wide screen to identify metastatic suppressors using primary human tumor cells in mice, which allows saturation screens. Using this unbiased approach, we have tested the hypothesis that endogenous colon cancer metastatic suppressors affect WNT-TCF signaling. Our screen has identified two novel metastatic suppressors: TMED3 and SOX12, the knockdown of which increases metastatic growth after direct seeding. Moreover, both modify the type of self-renewing spheroids, but only knockdown of TMED3 also induces spheroid cell spreading and lung metastases from a subcutaneous xenograft. Importantly, whereas TMED3 and SOX12 belong to different families involved in protein secretion and transcriptional regulation, both promote endogenous WNT-TCF activity. Treatments for advanced or metastatic colon cancer may thus not benefit from WNT blockers, and these may promote a worse outcome.

Indexed as

Signal TransductionAnimalsbeta CateninCell Line, TumorCell MovementColonColonic NeoplasmsGene Expression Regulation, NeoplasticGene Knockdown TechniquesGenomeHumansMiceNeoplasm MetastasisSOXC Transcription FactorsTCF Transcription FactorsVesicular Transport Proteinsbeta CateninSOX12 protein, humanSOXC Transcription FactorsTCF Transcription FactorsTMED3 protein, humanVesicular Transport ProteinsWnt Proteinscancerin vivo assaymetastatic suppressorWNT‐TCF

Identifiers

PMID24920608
PMCPMC4119353
OpenAlexW2013523306

What OpenQuestion holds

Textmetadata
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.