Evidence map›Paper›PMID 34916221›Full record

ArticleCancer research2022

An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression.

Manuel C Scheidmann, Francesc Castro-Giner, Karin Strittmatter, Ilona Krol, Aino Paasinen-Sohns, Ramona Scherrer, Cinzia Donato, Sofia Gkountela, Barbara M Szczerba, Zoi Diamantopoulou and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

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  9. Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025
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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

20 authors at 3 institutions in 1 country.

Manuel C ScheidmannDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Francesc Castro-GinerDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.ORCID 0000-0001-6111-0754
Karin StrittmatterDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Ilona KrolDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Aino Paasinen-SohnsDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Ramona ScherrerDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Cinzia DonatoDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Sofia GkountelaDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Barbara M SzczerbaDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Zoi DiamantopoulouDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Simone MuenstInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Tatjana VlajnicInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Leo KunzDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Marcus VetterDepartment of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Christoph RochlitzDepartment of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Verdon TaylorDepartment of Biomedicine, Embryology and Stem Cell Biology Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
Claudio GiachinoDepartment of Biomedicine, Embryology and Stem Cell Biology Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.ORCID 0000-0002-8332-0899
Timm SchroederDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Randall J PlattDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.ORCID 0000-0002-2914-7052
Nicola AcetoDepartment of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
University Hospital of Basel · CHETH Zurich · CHSIB Swiss Institute of Bioinformatics · CH

Funding

Basel Cancer League KLbB-4763-02-2019ETH Zürich PMB-01-16European Research Council #101001652European Union 801159-B2BSwiss Cancer League KLS-4518-08-2018Swiss Cancer League KLS-4834-08-2019Swiss National Science Foundation 163938Swiss National Science Foundation PP00P3_190077University of Basel and the ETH Zurich #101028567
6 · The paper itself

Abstract

Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process. Validation experiments revealed sensitivities to inhibitors that are already available, such as PLK1 inhibitors, to prevent CTC intravasation. Together, these findings present a new tool to reclassify driver genes involved in the spread of human cancer, providing insights into the biology of metastasis and paving the way to test targeted treatment approaches. SIGNIFICANCE: A loss-of-function CRISPR screen in human CTC-derived xenografts identifies genes critical for individual steps of the metastatic cascade, suggesting novel drivers and treatment opportunities for metastatic breast cancers.

Indexed as

AnimalsBiomarkers, TumorBreast NeoplasmsCell Cycle ProteinsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm MetastasisNeoplastic Cells, CirculatingBiomarkers, TumorCell Cycle ProteinsPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34916221
PMCPMC7612409
OpenAlexW4200511330

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.