Publications

Authors:

Crociani, O; Lastraioli, E; Boni, L; Pillozzi, S; Romoli, Mr; D'Amico, M; Stefanini, M; Crescioli, S; Taddei, A; Bencini, L; Bernini, M; Farsi, M; Beghelli, Stefania; Scarpa, Aldo; Messerini, L; Tomezzoli, Anna; Vindigni, C; Morgagni, P; Saragoni, L; Giommoni, E; Gasperoni, S; Di Costanzo, F; Roviello, F; DE MANZONI, Giovanni; Bechi, P; Arcangeli, A.

Title:

hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications.

Year:

2014

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

Sì

Name of journal:

Clinical Cancer Research

ISSN of journal:

1078-0432

N° Volume:

20

Number or Folder:

6

Page numbers:

1502-1512

Keyword:

bevacizumab, potassium channel HERG, potassium channel HERG1, unclassified drug, vasculotropin A; 1 [2 (6 methyl 2 pyridyl)ethyl] 4 (4 methylsulfonylaminobenzoyl)piperidine

Short description of contents:

PURPOSE: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. EXPERIMENTAL DESIGN: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. RESULTS: hERG1 was positive in 69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. CONCLUSION: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed.

Product ID:

81464

Handle IRIS:

11562/731363

Deposited On:

December 22, 2014

Last Modified:

November 15, 2022

Bibliographic citation:

Crociani, O; Lastraioli, E; Boni, L; Pillozzi, S; Romoli, Mr; D'Amico, M; Stefanini, M; Crescioli, S; Taddei, A; Bencini, L; Bernini, M; Farsi, M; Beghelli, Stefania; Scarpa, Aldo; Messerini, L; Tomezzoli, Anna; Vindigni, C; Morgagni, P; Saragoni, L; Giommoni, E; Gasperoni, S; Di Costanzo, F; Roviello, F; DE MANZONI, Giovanni; Bechi, P; Arcangeli, A., hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications. «Clinical Cancer Research» , vol. 20 , n. 6 , 2014 , pp. 1502-1512

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