Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
13 Sep 2022
Historique:
received: 01 08 2022
revised: 08 09 2022
accepted: 10 09 2022
entrez: 23 9 2022
pubmed: 24 9 2022
medline: 28 9 2022
Statut: epublish

Résumé

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.

Identifiants

pubmed: 36142530
pii: ijms231810623
doi: 10.3390/ijms231810623
pmc: PMC9504580
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
ERG1 Potassium Channel 0
Ether-A-Go-Go Potassium Channels 0
Integrin beta1 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Italian Association for Cancer Research
ID : 1662
Organisme : Italian Association for Cancer Research
ID : 15627
Organisme : Italian Association for Cancer Research
ID : 21510
Organisme : University of Florence
ID : N/A
Organisme : Ministry of Education, Universities and Research
ID : 20174TB8KW
Organisme : European Union
ID : 813834

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Auteurs

Jessica Iorio (J)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

Lorenzo Antonuzzo (L)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.

Emanuela Scarpi (E)

Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.

Massimo D'Amico (M)

DI.V.A.L Toscana Srl, 50019 Sesto Fiorentino, Italy.

Claudia Duranti (C)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

Luca Messerini (L)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

Clotilde Sparano (C)

Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.

Damiano Caputo (D)

General Surgery, Campus Bio-Medico University, 00128 Rome, Italy.
Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.

Daniele Lavacchi (D)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.

Domenico Borzomati (D)

General Surgery, Campus Bio-Medico University, 00128 Rome, Italy.
Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.

Alice Antonelli (A)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.

Lorenzo Nibid (L)

Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
Pathology Unit, Campus Bio-Medico University, 00128 Rome, Italy.

Giuseppe Perrone (G)

Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
Pathology Unit, Campus Bio-Medico University, 00128 Rome, Italy.

Alessandro Coppola (A)

General Surgery, Campus Bio-Medico University, 00128 Rome, Italy.
Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.

Roberto Coppola (R)

General Surgery, Campus Bio-Medico University, 00128 Rome, Italy.
Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.

Francesco di Costanzo (F)

Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.

Elena Lastraioli (E)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Complex Dynamics Study Centre (CSDC), University of Florence, 50100 Florence, Italy.

Annarosa Arcangeli (A)

Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Complex Dynamics Study Centre (CSDC), University of Florence, 50100 Florence, Italy.

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