Evidence map›Paper›PMID 38169150›Full record

SynthesisAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression.

Sara P Cruz, Qin Zhang, Raman Devarajan, Christos Paia, Binjie Luo, Kai Zhang, Saara Koivusalo, Longguang Qin, Jihan Xia, Anne Ahtikoski and 4 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
6.7field-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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

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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

14 authors at 4 institutions in 3 countries.

Sara P CruzDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Qin ZhangDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Raman DevarajanDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Christos PaiaDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Binjie LuoDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Kai ZhangDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Saara KoivusaloDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Longguang QinDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Jihan XiaDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Anne AhtikoskiDepartments of Urology, Pathology and Radiology, and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Markku VaaralaDepartments of Urology, Pathology and Radiology, and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Tomasz WentaDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Gong-Hong WeiDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.
Aki ManninenDisease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5a, Oulu, 90220, Finland.ORCID 0000-0002-6263-8101
University of Oulu · FIOulu University Hospital · FIShanghai Medical College of Fudan University · CNUniversity of Gdańsk · PL

Funding

Academy of Finland 311934Cancer Foundation Finland (GHW, AM)Finnish Cancer InstituteJane and Aatos Erkko foundationJane ja Aatos Erkon Säätiö 190046National Natural Science Foundation of China 82073082/GHWNational Natural Science Foundation of China 82311530050National Natural Science Foundation of China 82311530050/GHWResearch Council of Finland 251314/AMSigrid Juséliuksen SäätiöSigrid Jusélius Foundation (GHW)Syöpäsäätiö 61-6158Terveyden Tutkimuksen Toimikunta 311934
6 · The paper itself

Abstract

The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta-analysis of multiple PCa cohorts is performed which revealed that downregulation or genomic loss of ITGA1 and ITGA2 integrin genes is associated with tumor progression and worse prognosis. Genomic deletion of both ITGA1 and ITGA2 activated epithelial-to-mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potential in vitro and converting them into tumorigenic cells in vivo. Mechanistically, EMT is induced by enhanced secretion and autocrine activation of TGFβ1 and nuclear targeting of YAP1. An unbiased genome-wide co-expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator of ITGA1 and ITGA2 expression in PCa cells while TEAD1 loss phenocopied the dual loss of α1- and α2-integrins in vitro and in vivo. Remarkably, clinical data analysis revealed that TEAD1 downregulation or genomic loss is associated with aggressive PCa and together with low ITGA1 and ITGA2 expression synergistically impacted PCa prognosis and progression. This study thus demonstrated that loss of α1- and α2-integrins, either via deletion/inactivation of the ITGA1/ITGA2 locus or via loss of TEAD1, contributes to PCa progression by inducing TGFβ1-driven EMT.

Indexed as

ProstateProstatic NeoplasmsCell Line, TumorHumansIntegrin alpha2MaleSignal TransductionTEA Domain Transcription FactorsIntegrin alpha2TEAD1 protein, humanTEA Domain Transcription FactorsECMEMTepitheliumintegrinprostate

Identifiers

PMID38169150
PMCPMC10953553
OpenAlexW4390542937

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.