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Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer

BACKGROUND: Integrins play a critical role in carcinogenesis. Integrin β1 localization is regulated by the guanosine-5′-triphosphate hydrolase Rab25 and integrin β1 levels are elevated in the serum of colon cancer patients; thus, the present study examined the effects of epidermal growth factor (EGF...

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Autores principales: Hong, Kyung Sook, Jeon, Eun-Young, Chung, Soon Sup, Kim, Kwang Ho, Lee, Ryung-Ah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836438/
https://www.ncbi.nlm.nih.gov/pubmed/29515334
http://dx.doi.org/10.1186/s12935-018-0526-y
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author Hong, Kyung Sook
Jeon, Eun-Young
Chung, Soon Sup
Kim, Kwang Ho
Lee, Ryung-Ah
author_facet Hong, Kyung Sook
Jeon, Eun-Young
Chung, Soon Sup
Kim, Kwang Ho
Lee, Ryung-Ah
author_sort Hong, Kyung Sook
collection PubMed
description BACKGROUND: Integrins play a critical role in carcinogenesis. Integrin β1 localization is regulated by the guanosine-5′-triphosphate hydrolase Rab25 and integrin β1 levels are elevated in the serum of colon cancer patients; thus, the present study examined the effects of epidermal growth factor (EGF) and Rab25 on integrin β1 localization in colon cancer cells. METHODS: HCT116 human colon cancer cells were treated with increasing concentrations of EGF, and cell proliferation and protein expression were monitored by MTT and western blot analyses, respectively. Cell fractionation was performed to determine integrin β1 localization in the membrane and cytosol. Integrin β1 extracellular shedding was monitored by enzyme-linked immunosorbent assays (ELISAs) with culture supernatants from stimulated cells. HCT116 cells were transfected with Rab25-specific siRNA to determine the significance of Rab25 in integrin β1 trafficking in the presence of EGF. RESULTS: Total integrin β1 expression increased in response to EGF and subsequently decreased at 24 h post-stimulation. A similar decrease was observed in purified membrane fractions, whereas no changes were observed in cytosolic levels. ELISAs using media from stimulated cell cultures demonstrated increased integrin β1 levels corresponding to the decrease observed in membrane fractions, suggesting that EGF induces integrin receptor shedding. EGF stimulation in Rab25-knockdown cells resulted in integrin β1 accumulation in the membrane, suggesting that Rab25 promotes integrin endocytosis. CONCLUSIONS: Integrin β1 is shed from colon cancer cells in response to EGF stimulation in a Rab25-dependent manner. These results further the present understanding of the role of integrin β1 in colon cancer progression.
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spelling pubmed-58364382018-03-07 Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer Hong, Kyung Sook Jeon, Eun-Young Chung, Soon Sup Kim, Kwang Ho Lee, Ryung-Ah Cancer Cell Int Primary Research BACKGROUND: Integrins play a critical role in carcinogenesis. Integrin β1 localization is regulated by the guanosine-5′-triphosphate hydrolase Rab25 and integrin β1 levels are elevated in the serum of colon cancer patients; thus, the present study examined the effects of epidermal growth factor (EGF) and Rab25 on integrin β1 localization in colon cancer cells. METHODS: HCT116 human colon cancer cells were treated with increasing concentrations of EGF, and cell proliferation and protein expression were monitored by MTT and western blot analyses, respectively. Cell fractionation was performed to determine integrin β1 localization in the membrane and cytosol. Integrin β1 extracellular shedding was monitored by enzyme-linked immunosorbent assays (ELISAs) with culture supernatants from stimulated cells. HCT116 cells were transfected with Rab25-specific siRNA to determine the significance of Rab25 in integrin β1 trafficking in the presence of EGF. RESULTS: Total integrin β1 expression increased in response to EGF and subsequently decreased at 24 h post-stimulation. A similar decrease was observed in purified membrane fractions, whereas no changes were observed in cytosolic levels. ELISAs using media from stimulated cell cultures demonstrated increased integrin β1 levels corresponding to the decrease observed in membrane fractions, suggesting that EGF induces integrin receptor shedding. EGF stimulation in Rab25-knockdown cells resulted in integrin β1 accumulation in the membrane, suggesting that Rab25 promotes integrin endocytosis. CONCLUSIONS: Integrin β1 is shed from colon cancer cells in response to EGF stimulation in a Rab25-dependent manner. These results further the present understanding of the role of integrin β1 in colon cancer progression. BioMed Central 2018-03-05 /pmc/articles/PMC5836438/ /pubmed/29515334 http://dx.doi.org/10.1186/s12935-018-0526-y Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Hong, Kyung Sook
Jeon, Eun-Young
Chung, Soon Sup
Kim, Kwang Ho
Lee, Ryung-Ah
Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title_full Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title_fullStr Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title_full_unstemmed Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title_short Epidermal growth factor-mediated Rab25 pathway regulates integrin β1 trafficking in colon cancer
title_sort epidermal growth factor-mediated rab25 pathway regulates integrin β1 trafficking in colon cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836438/
https://www.ncbi.nlm.nih.gov/pubmed/29515334
http://dx.doi.org/10.1186/s12935-018-0526-y
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