Evidence map›Paper›PMID 30325918›Full record

ArticlePLoS genetics2018

A genome-wide Drosophila epithelial tumorigenesis screen identifies Tetraspanin 29Fb as an evolutionarily conserved suppressor of Ras-driven cancer.

Tamara Zoranovic, Jan Manent, Lee Willoughby, Ricardo Matos de Simoes, John E La Marca, Sofya Golenkina, Xia Cuiping, Susanne Gruber, Belinda Angjeli, Elisabeth Eva Kanitz and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. CRIF counteracts oncogenic Ras and regulates heterochromatin.Molecular genetics and genomics : MGG · 2025
    Article
  2. Article
  3. Review
  4. RNA Interference (RNAi) Screening in Cultured Drosophila Cells.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  5. Article
  6. Review
  7. Article
  8. 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

18 authors at 6 institutions in 3 countries.

Tamara ZoranovicIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Jan ManentResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID 0000-0001-9152-5459
Lee WilloughbyResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Ricardo Matos de SimoesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0002-1700-5276
John E La MarcaDepartment of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.ORCID 0000-0001-6442-9947
Sofya GolenkinaDepartment of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Xia CuipingIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Susanne GruberIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Belinda AngjeliIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Elisabeth Eva KanitzIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Shane J F CroninIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
G Gregory NeelyIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.ORCID 0000-0003-2809-6457
Andreas WernitznigBoehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Patrick O HumbertResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Kaylene J SimpsonSir Peter MacCallum Department of Oncology, Department of Anatomy & Neuroscience, Department of Biochemistry & Molecular Biology, and Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia.
Constantine S MitsiadesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
Helena E RichardsonResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID 0000-0003-3852-4953
Josef M PenningerIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Campus Vienna BioCentre, Vienna, Austria.
Institute of Molecular Biotechnology · ATLa Trobe University · AUThe University of Melbourne · AUHarvard University · USBoehringer Ingelheim (Austria) · ATPeter MacCallum Cancer Centre · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, Ras mutations alone are insufficient for tumorigenesis, therefore it is paramount to identify cooperating cancer-relevant signaling pathways. We devised an in vivo near genome-wide, functional screen in Drosophila and discovered multiple novel, evolutionarily-conserved pathways controlling Ras-driven epithelial tumorigenesis. Human gene orthologs of the fly hits were significantly downregulated in thousands of primary tumors, revealing novel prognostic markers for human epithelial tumors. Of the top 100 candidate tumor suppressor genes, 80 were validated in secondary Drosophila assays, identifying many known cancer genes and multiple novel candidate genes that cooperate with Ras-driven tumorigenesis. Low expression of the confirmed hits significantly correlated with the KRASG12 mutation status and poor prognosis in pancreatic cancer. Among the novel top 80 candidate cancer genes, we mechanistically characterized the function of the top hit, the Tetraspanin family member Tsp29Fb, revealing that Tsp29Fb regulates EGFR signaling, epithelial architecture and restrains tumor growth and invasion. Our functional Drosophila screen uncovers multiple novel and evolutionarily conserved epithelial cancer genes, and experimentally confirmed Tsp29Fb as a key regulator of EGFR/Ras induced epithelial tumor growth and invasion.

Indexed as

AnimalsAnimals, Genetically ModifiedCarcinogenesisDrosophila melanogasterDrosophila ProteinsEpithelial CellsFemaleGenes, rasGenetic TestingHumansIMP DehydrogenaseMaleMiceNeoplasmsOncogenesSignal TransductionDrosophila ProteinsIMP Dehydrogenaseras protein, DrosophilaTetraspanin 29Tumor Suppressor Proteins

Identifiers

PMID30325918
PMCPMC6203380
OpenAlexW2896550859

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.