Evidence map›Paper›PMID 27765911›Full record

ArticleOncotarget2016

Integrin α2β1 inhibits MST1 kinase phosphorylation and activates Yes-associated protein oncogenic signaling in hepatocellular carcinoma.

Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
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  9. Article
  10. Integrins in cancer stem cells.Frontiers in cell and developmental biology · 2024
    Review
  11. Article
  12. Review
  13. Effect of Inactivation ofJournal of the Endocrine Society · 2022
    Article
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  16. Article
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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

5 authors at 4 institutions in 3 countries.

Kwong-Fai WongDepartment of Pharmacology, National University Health System, Singapore.
Angela M LiuDepartment of Pharmacology, National University Health System, Singapore.
Wanjin HongInstitute of Molecular and Cell Biology, Biopolis, Singapore.
Zhi XuDepartment of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
John M LukDepartment of Pharmacology, National University Health System, Singapore.
National University Health System · SGInstitute of Molecular and Cell Biology · SGNanjing Medical University · CNQueen Mary Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities. Knockdown of integrin α2 gene (ITGA2) suppressed YAP targeted gene expression in vitro. α2β1 and collagen binding resulted in suppressing Hippo signaling of mammalian sterile 20-like kinase 1 (MST1) and Large tumor suppressor homolog 1 (LATS1) with concomitant activation of YAP-mediated connective tissue growth factor (CTGF) gene expression. In vitro kinase assay showed that MST1 is an immediate downstream target of integrin α2 with S1180 residue as the critical phosphorylation site. Clinical correlational analysis using a gene expression dataset of 228 HCC tumors revealed that ITGA2 expression was significantly associated with tumor progression, and co-expression with YAP targeted genes (AXL receptor tyrosine kinase, CTGF, cyclin D1, glypican 3, insulin like growth factor 1 receptor, and SRY-box 4) correlated with survivals of HCC patients. In conclusion, α2β1 integrin activation through cellular adhesion impacts the Hippo pathway in solid tumors and modulates MST1-YAP signaling cascade. Targeting integrin α2 holds promises for treating YAP-positive HCC.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, HepatocellularCell AdhesionCell Line, TumorConnective Tissue Growth FactorFemaleHumansIntegrin alpha2Integrin beta1Liver NeoplasmsMalePhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesSerineSignal TransductionAdaptor Proteins, Signal TransducingCCN2 protein, humanConnective Tissue Growth FactorIntegrin alpha2Integrin beta1LATS1 protein, humanmammalian sterile 20-like kinase 1, humanPhosphoproteinsProtein Serine-Threonine KinasesSerineTranscription FactorsYAP1 protein, humanYAP-Signaling Proteinsextracellular stimulihippo pathwayliver cancerMST1Yes-associated protein

Identifiers

PMID27765911
PMCPMC5363613
OpenAlexW2535463508

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.