RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer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 β1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the huma...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2013-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/srep03308 |
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| author | Olivia Crociani Francesca Zanieri Serena Pillozzi Elena Lastraioli Matteo Stefanini Antonella Fiore Angelo Fortunato Massimo D'Amico Marika Masselli Emanuele De Lorenzo Luca Gasparoli Martina Chiu Ovidio Bussolati Andrea Becchetti Annarosa Arcangeli |
| author_facet | Olivia Crociani Francesca Zanieri Serena Pillozzi Elena Lastraioli Matteo Stefanini Antonella Fiore Angelo Fortunato Massimo D'Amico Marika Masselli Emanuele De Lorenzo Luca Gasparoli Martina Chiu Ovidio Bussolati Andrea Becchetti Annarosa Arcangeli |
| author_sort | Olivia Crociani |
| collection | DOAJ |
| description | 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 β1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the human ether-à-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. |
| format | Article |
| id | doaj-art-fc2a592984f04cb7a2868137547db41e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2013-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-fc2a592984f04cb7a2868137547db41e2025-02-02T12:25:39ZengNature PortfolioScientific Reports2045-23222013-11-013111310.1038/srep03308RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancerOlivia Crociani0Francesca Zanieri1Serena Pillozzi2Elena Lastraioli3Matteo Stefanini4Antonella Fiore5Angelo Fortunato6Massimo D'Amico7Marika Masselli8Emanuele De Lorenzo9Luca Gasparoli10Martina Chiu11Ovidio Bussolati12Andrea Becchetti13Annarosa Arcangeli14Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)Unit of General Pathology Department of Biomedical, Biotechnological and Translational Sciences (SBiBiT) University of ParmaUnit of General Pathology Department of Biomedical, Biotechnological and Translational Sciences (SBiBiT) University of ParmaDepartment of Biotechnology and Biosciences, University of Milano BicoccaDepartment of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence and Istituto Toscano Tumori (ITT)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 β1 integrin-mediated adhesion and leads to VEGF-A secretion. The effect is modulated by the human ether-à-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.https://doi.org/10.1038/srep03308 |
| spellingShingle | Olivia Crociani Francesca Zanieri Serena Pillozzi Elena Lastraioli Matteo Stefanini Antonella Fiore Angelo Fortunato Massimo D'Amico Marika Masselli Emanuele De Lorenzo Luca Gasparoli Martina Chiu Ovidio Bussolati Andrea Becchetti Annarosa Arcangeli RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer Scientific Reports |
| title | RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| title_full | RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| title_fullStr | RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| title_full_unstemmed | RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| title_short | RETRACTED ARTICLE: hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| title_sort | retracted article herg1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer |
| url | https://doi.org/10.1038/srep03308 |
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