دورية أكاديمية
أعرض في EDS

A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia.

التفاصيل البيبلوغرافية
العنوان: A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia.
المؤلفون: Middonti E; Department of Oncology, University of Torino, 10043, Orbassano, Italy. Emanuele.middonti@unito.it.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy. Emanuele.middonti@unito.it., Astanina E; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy., Vallariello E; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy., Hoza RM; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy., Metovic J; Department of Oncology, University of Torino, 10043, Orbassano, Italy., Spadi R; SC Oncologia Medica, Città della Salute e della Scienza di Torino, 10126, Torino, Italy., Cristiano C; SC Oncologia Medica, Città della Salute e della Scienza di Torino, 10126, Torino, Italy., Papotti M; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Division of Pathology at Città della Salute e della Scienza di Torino, 10126, Torino, Italy., Allavena P; IRCCS, Humanitas Clinical and Research Center, 20089, Rozzano, Italy., Novelli F; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.; Laboratory of Tumor Immunology, Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, 10126, Torino, Italy.; Molecular Biotechnology Center, University of Torino, 10125, Torino, Italy., Parab S; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy., Cappello P; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.; Laboratory of Tumor Immunology, Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, 10126, Torino, Italy.; Molecular Biotechnology Center, University of Torino, 10125, Torino, Italy., Scarpa A; Applied Research Center (ARC-NET), University of Verona, 37134, Verona, Italy.; Department of Diagnostics and Public Health, University of Verona, 37134, Verona, Italy., Lawlor R; Applied Research Center (ARC-NET), University of Verona, 37134, Verona, Italy.; Department of Diagnostics and Public Health, University of Verona, 37134, Verona, Italy., Di Maio M; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Medical Oncology, Ordine Mauriziano Hospital, 10128, Torino, Italy., Arese M; Department of Oncology, University of Torino, 10043, Orbassano, Italy.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy., Bussolino F; Department of Oncology, University of Torino, 10043, Orbassano, Italy. Federico.Bussolino@unito.it.; Candiolo Cancer Institute-IRCCS-FPO, 10060, Candiolo, Italy. Federico.Bussolino@unito.it.
المصدر: EMBO reports [EMBO Rep] 2024 Apr; Vol. 25 (4), pp. 1886-1908. Date of Electronic Publication: 2024 Feb 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Blackwell Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : London, UK : Wiley Blackwell
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
مواضيع طبية MeSH: Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/pathology , Carcinoma, Pancreatic Ductal*/genetics , Carcinoma, Pancreatic Ductal*/pathology , Carcinoma in Situ*/pathology, Humans ; Neuroligins ; Cell Transformation, Neoplastic
مستخلص: Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a dismal prognosis that arises from precursor lesions called pancreatic intraepithelial neoplasias (PanINs). Progression from low- to high-grade PanINs is considered as tumor initiation, and a deeper understanding of this switch is needed. Here, we show that synaptic molecule neuroligin-2 (NLGN2) is expressed by pancreatic exocrine cells and plays a crucial role in the regulation of contact inhibition and epithelial polarity, which characterize the switch from low- to high-grade PanIN. NLGN2 localizes to tight junctions in acinar cells, is diffusely distributed in the cytosol in low-grade PanINs and is lost in high-grade PanINs and in a high percentage of advanced PDACs. Mechanistically, NLGN2 is necessary for the formation of the PALS1/PATJ complex, which in turn induces contact inhibition by reducing YAP function. Our results provide novel insights into NLGN2 functions outside the nervous system and can be used to model PanIN progression.
(© 2024. The Author(s).)
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معلومات مُعتمدة: grants 22910,12182 and 18652 Fondazione AIRC per la ricerca sul cancro ETS (AIRC); IG 19931 Fondazione AIRC per la ricerca sul cancro ETS (AIRC); PRIN 2017,grant 2017237P5X,PRIN 2022 grant 2022HREZJT,PNRR 3F 4 Health Ministero dell'Università e della Ricerca (MUR); Proactive FPRC 5xmille MIUR; Bando Ricerca Locale 2019 AREM_RILO_19_01; Fondo CD38 and Fondo Ursula e Giorgio Cytron Fondazione Ricerca Molinette (Fondazione Ricerca Tumori Molinette); no. 2020.0719 Fondazione CRT (CRT Foundation)
فهرسة مساهمة: Keywords: Cell Polarity; Contact Inhibition; Neuroligin; Pancreatic Intraepithelial Neoplasia; YAP
المشرفين على المادة: 0 (Neuroligins)
تواريخ الأحداث: Date Created: 20240227 Date Completed: 20240415 Latest Revision: 20240520
رمز التحديث: 20240521
مُعرف محوري في PubMed: PMC11014856
DOI: 10.1038/s44319-024-00104-x
PMID: 38413734
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-3178
DOI:10.1038/s44319-024-00104-x