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Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway
BACKGROUND: Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833032/ https://www.ncbi.nlm.nih.gov/pubmed/29499765 http://dx.doi.org/10.1186/s13046-018-0718-2 |
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author | Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun |
author_facet | Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun |
author_sort | Hu, Xiang |
collection | PubMed |
description | BACKGROUND: Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression. METHODS: The tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis. The effect of OGN on cell proliferation and tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay, immunofluorescence analysis and internalization assay were used for mechanistic study. RESULTS: Patients with high expression of OGN were associated with a profound longer survival in CRC and the high serum OGN level was also indicative of fewer recurrences consistently. In colon cancer cells, OGN increased dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment of downstream components of the EGFR internalization machinery (Eps15 and epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to inhibition of epithelial-mesenchymal transition. As results, in vitro and in vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit invasion of colon cancer cells then impede cancer progression. CONCLUSIONS: There is a positive association between OGN level and prolonged survival in CRC. OGN plays a restrictive role in colorectal cancer progression by reduced activation of EGFR/AKT/Zeb-1. |
format | Online Article Text |
id | pubmed-5833032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58330322018-03-05 Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun J Exp Clin Cancer Res Research BACKGROUND: Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression. METHODS: The tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis. The effect of OGN on cell proliferation and tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay, immunofluorescence analysis and internalization assay were used for mechanistic study. RESULTS: Patients with high expression of OGN were associated with a profound longer survival in CRC and the high serum OGN level was also indicative of fewer recurrences consistently. In colon cancer cells, OGN increased dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment of downstream components of the EGFR internalization machinery (Eps15 and epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to inhibition of epithelial-mesenchymal transition. As results, in vitro and in vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit invasion of colon cancer cells then impede cancer progression. CONCLUSIONS: There is a positive association between OGN level and prolonged survival in CRC. OGN plays a restrictive role in colorectal cancer progression by reduced activation of EGFR/AKT/Zeb-1. BioMed Central 2018-03-02 /pmc/articles/PMC5833032/ /pubmed/29499765 http://dx.doi.org/10.1186/s13046-018-0718-2 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 | Research Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title | Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title_full | Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title_fullStr | Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title_full_unstemmed | Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title_short | Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway |
title_sort | osteoglycin (ogn) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via egfr/akt pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833032/ https://www.ncbi.nlm.nih.gov/pubmed/29499765 http://dx.doi.org/10.1186/s13046-018-0718-2 |
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