@article{8acf75814e1a479e89086c7457e0ff6a,
title = "Herg1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer",
abstract = "Angiogenesis is a potential target for cancer therapy. We identified a novel signaling pathway that sustains angiogenesis and progression in colorectal cancer (CRC). This pathway is triggered by β 1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the human ether-{\`a}-go-go related gene 1 (Herg1) K + channel. Herg1 recruits and activates PI3K and Akt. This in turn increases the Hypoxia Inducible Factor (HIF)-dependent transcription of VEGF-A and other tumour progression genes. This signaling pathway has novel features in that the integrin-and Herg1-dependent activation of HIF (i) is triggered in normoxia, especially after CRC cells have experienced a hypoxic stage, (ii) involves NF-kB and (iii) is counteracted by an active p53. Blocking Herg1 switches this pathway off also in vivo, by inhibiting cell growth, angiogenesis and metastatic spread. This suggests that non-cardiotoxic anti-Herg1 drugs might be a fruitful therapeutic strategy to prevent the failure of anti-VEGF therapy.",
author = "Olivia Crociani and Francesca Zanieri and Serena Pillozzi and Elena Lastraioli and Matteo Stefanini and Antonella Fiore and Angelo Fortunato and Massimo D'Amico and Marika Masselli and {De Lorenzo}, Emanuele and Luca Gasparoli and Martina Chiu and Ovidio Bussolati and Andrea Becchetti and Annarosa Arcangeli",
note = "Funding Information: Grant Support: Associazione Italiana per la Ricerca sul Cancro (AIRC), Association for International Cancer Research (AICR), Istituto Toscano Tumori (ITT), Associazione Genitori Noi per Voi, Fondazione Bartolomei, Ente Cassa di Risparmio di Firenze and PRIN 2006 to AA. FAR (University of Milano-Bicocca) to AB. We thank Dr. A Giaccia (Stanford University School of Medicine, Stanford, USA) for the kind gift of the hypoxia responsive element-luciferase reporter gene vector, Dr. M. Belatti and Prof. A. Nassi (Department of Biochemistry, University of Florence, Italy) for allowing the use of the Luminometer. We also thank Dr. Rita Falcioni (Department of Experimental Oncology, Istituto Nazionale Tumori Regina Elena IRCCSO, Roma) for providing us WT and p53-/-HCT116 cells.",
year = "2013",
doi = "10.1038/srep03308",
language = "English (US)",
volume = "3",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}