RT Journal Article SR Electronic T1 DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1465 OP 1476 DO 10.1136/gutjnl-2018-316128 VO 68 IS 8 A1 Jeroni Luna A1 Jacopo Boni A1 Miriam Cuatrecasas A1 Xavier Bofill-De Ros A1 Estela Núñez-Manchón A1 Meritxell Gironella A1 Eva C Vaquero A1 Maria L Arbones A1 Susana de la Luna A1 Cristina Fillat YR 2019 UL http://gut.bmj.com/content/68/8/1465.abstract AB 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.