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VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells
The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888064/ https://www.ncbi.nlm.nih.gov/pubmed/31717527 http://dx.doi.org/10.3390/ijms20225608 |
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author | Nagano, Hikaru Tomida, Chisato Yamagishi, Naoko Teshima-Kondo, Shigetada |
author_facet | Nagano, Hikaru Tomida, Chisato Yamagishi, Naoko Teshima-Kondo, Shigetada |
author_sort | Nagano, Hikaru |
collection | PubMed |
description | The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports tumor cell growth in an angiogenesis-dependent manner. In this study, we found angiogenesis-independent novel crosstalk between the VEGF and the EGF pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor (PlGF) activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF/EGF receptor (EGF-R)-dependent manner. Mechanistically, VEGFR-1 interacted with and stabilized EGF-R, leading to increased EGF-R protein levels and prolonged its expression on cell surface plasma membrane. In contrast, VEGFR-1 blockade by a neutralizing antibody and an antagonistic peptide of VEGFR-1 suppressed the complex formation of VEGFR-1 and EGF-R and decreased EGF-R expression via a lysosome-dependent pathway, resulting in the suppression of proliferation activity. Our results indicated that VEGFR-1 regulated EGF-R expression to promote proliferation activity in a cell-autonomous-dependent manner. |
format | Online Article Text |
id | pubmed-6888064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68880642019-12-09 VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells Nagano, Hikaru Tomida, Chisato Yamagishi, Naoko Teshima-Kondo, Shigetada Int J Mol Sci Article The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports tumor cell growth in an angiogenesis-dependent manner. In this study, we found angiogenesis-independent novel crosstalk between the VEGF and the EGF pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor (PlGF) activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF/EGF receptor (EGF-R)-dependent manner. Mechanistically, VEGFR-1 interacted with and stabilized EGF-R, leading to increased EGF-R protein levels and prolonged its expression on cell surface plasma membrane. In contrast, VEGFR-1 blockade by a neutralizing antibody and an antagonistic peptide of VEGFR-1 suppressed the complex formation of VEGFR-1 and EGF-R and decreased EGF-R expression via a lysosome-dependent pathway, resulting in the suppression of proliferation activity. Our results indicated that VEGFR-1 regulated EGF-R expression to promote proliferation activity in a cell-autonomous-dependent manner. MDPI 2019-11-09 /pmc/articles/PMC6888064/ /pubmed/31717527 http://dx.doi.org/10.3390/ijms20225608 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nagano, Hikaru Tomida, Chisato Yamagishi, Naoko Teshima-Kondo, Shigetada VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title | VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title_full | VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title_fullStr | VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title_full_unstemmed | VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title_short | VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells |
title_sort | vegfr-1 regulates egf-r to promote proliferation in colon cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888064/ https://www.ncbi.nlm.nih.gov/pubmed/31717527 http://dx.doi.org/10.3390/ijms20225608 |
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