Evidence map›Paper›PMID 25774502›Full record

ArticleThe Journal of clinical investigation2015

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.

Wies van Roosmalen, Sylvia E Le Dévédec, Ofra Golani, Marcel Smid, Irina Pulyakhina, Annemieke M Timmermans, Maxime P Look, Di Zi, Chantal Pont, Marjo de Graauw and 8 more

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In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.

  1. Pooled it
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  16. SRPKs: a promising therapeutic target in cancer.Clinical and experimental medicine · 2023
    Review
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  19. Article
  20. Review

30 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

18 authors at 4 institutions in 2 countries.

Wies van Roosmalen
Sylvia E Le Dévédec
Ofra Golani
Marcel Smid
Irina Pulyakhina
Annemieke M Timmermans
Maxime P Look
Di Zi
Chantal Pont
Marjo de Graauw
Suha Naffar-Abu-Amara
Catherine Kirsanova
Gabriella Rustici
Peter A C 't Hoen
John W M Martens
John A Foekens
Benjamin Geiger
Bob van de Water
Leiden University · NLWeizmann Institute of Science · ILLeiden University Medical Center · NLCentre for Human Drug Research · NL

Funding

European Research Council 294852
6 · The paper itself

Abstract

Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.

Indexed as

AnimalsBone NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungCell AdhesionCell MovementCell PolarityFemaleFocal AdhesionsGene Expression Regulation, NeoplasticGenetic Association StudiesHumansKaplan-Meier EstimateLung NeoplasmsMiceNeoplasm MetastasisITGB3BP protein, humanNeoplasm ProteinsNF-kappa BNuclear ProteinsProtein Serine-Threonine KinasesRNA, Small InterferingSRPK1 protein, humanSrpk1 protein, mouse

Identifiers

PMID25774502
PMCPMC4396474
OpenAlexW2000759232

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.