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Analysis of institutional authors

Cuatrecasas MAuthorBofill-De Ros XAuthorNúñez-Manchón EAuthorGironella MAuthorVaquero, EcAuthorDe La Luna SCorresponding AuthorFillat CCorresponding Author

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Article

DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth

Publicated to:Gut. 68 (8): 1465-1476 - 2019-08-01 68(8), DOI: 10.1136/gutjnl-2018-316128

Authors: Luna, Jeroni; Boni, Jacopo; Cuatrecasas, Miriam; Bofill-De Ros, Xavier; Nunez-Manchon, Estela; Gironella, Meritxell; Vaquero, Eva C; Arbones, Maria L; de la Luna, Susana; Fillat, Cristina

Affiliations

Banc Tumors Biobanc Clin IDIBAPS, Barcelona, Spain - Author
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain - Author
Barcelona Institute of Science and Technology (BIST) - Author
CIBER Enfermedades Hepáticas y Digestivas - Author
CIBER Enfermedades Raras - Author
CSIC - Instituto de Biologia Molecular de Barcelona (IBMB) - Author
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain - Author
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Patol, CDB, Barcelona, Spain - Author
Hospital Clinic Barcelona - Author
IBMB, Barcelona, Spain - Author
ICREA, Barcelona, Spain - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain - Author
Institució Catalana de Recerca i Estudis Avançats - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
UB, Barcelona, Spain - Author
Universitat de Barcelona - Author
Universitat Pompeu Fabra Barcelona - Author
UPF, Barcelona, Spain - Author
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Abstract

© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ. Background and aims: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumour with a poor prognosis using current treatments. Targeted therapies may offer a new avenue for more effective strategies. Dual-specificity tyrosine regulated kinase 1A (DYRK1A) is a pleiotropic kinase with contradictory roles in different tumours that is uncharacterised in PDAC. Here, we aimed to investigate the role of DYRK1A in pancreatic tumorigenesis. Design: We analysed DYRK1A expression in PDAC genetic mouse models and in patient samples. DYRK1A function was assessed with knockdown experiments in pancreatic tumour cell lines and in PDAC mouse models with genetic reduction of Dyrk1a dosage. Furthermore, we explored a mechanistic model for DYRK1A activity. Results: We showed that DYRK1A was highly expressed in PDAC, and that its protein level positively correlated with that of c-MET. Inhibition of DYRK1A reduced tumour progression by limiting tumour cell proliferation. DYRK1A stabilised the c-MET receptor through SPRY2, leading to prolonged activation of extracellular signal-regulated kinase signalling. Conclusions: These findings reveal that DYRK1A contributes to tumour growth in PDAC, at least through regulation of c-MET accumulation, suggesting that inhibition of DYRK1A could represent a novel therapeutic target for PDAC.

Keywords

cancercarcinogenesiscell growthcell-survivalinactivationinhibitionmirk/dyrk1bmolecular mechanismsregulatorsresponsessubtypesup-regulationAdenocarcinomaAnimalsCancerCarcinogenesisCarcinoma, pancreatic ductalCell growthCell line, tumorCell proliferationCell-survivalDyrk kinasesFibroblast growth factorsGene expression regulation, neoplasticHumansInactivationInhibitionIntracellular signaling peptides and proteinsMembrane proteinsMiceMirk/dyrk1bMolecular mechanismsPancreatic cancerPancreatic neoplasmsProtein serine-threonine kinasesProtein-kinasesProtein-tyrosine kinasesProto-oncogene proteins c-metRegulatorsResponsesSignal transductionSpry2 protein, humanSpry2 protein, mouseSubtypesUp-regulation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Gut due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 3/88, thus managing to position itself as a Q1 (Primer Cuartil), in the category Gastroenterology & Hepatology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.92. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.3 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 12.29 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-13, the following number of citations:

  • WoS: 51
  • Scopus: 53
  • Europe PMC: 33
  • OpenCitations: 54

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 60.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 60 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 22.5.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Luna J) and Last Author (Fillat Fonts, Cristina).

the authors responsible for correspondence tasks have been Luna Cornado, Jeronimo and Fillat Fonts, Cristina.