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In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cel...

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Autores principales: Wei, Ran, Wong, Janet Pik Ching, Lyu, Peng, Xi, Xinping, Tong, Olivia, Zhang, Shu‐Dong, Yuen, Hiu Fung, Shirasawa, Senji, Kwok, Hang Fai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111822/
https://www.ncbi.nlm.nih.gov/pubmed/29851214
http://dx.doi.org/10.1111/jcmm.13686
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author Wei, Ran
Wong, Janet Pik Ching
Lyu, Peng
Xi, Xinping
Tong, Olivia
Zhang, Shu‐Dong
Yuen, Hiu Fung
Shirasawa, Senji
Kwok, Hang Fai
author_facet Wei, Ran
Wong, Janet Pik Ching
Lyu, Peng
Xi, Xinping
Tong, Olivia
Zhang, Shu‐Dong
Yuen, Hiu Fung
Shirasawa, Senji
Kwok, Hang Fai
author_sort Wei, Ran
collection PubMed
description Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser extent in KRAS wild‐type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E‐cadherin in KRAS mutant cells. In human CRC specimens, a high‐level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E‐cadherin expression. Furthermore, we have found that 15 genes were co‐upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.
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spelling pubmed-61118222018-09-01 In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer Wei, Ran Wong, Janet Pik Ching Lyu, Peng Xi, Xinping Tong, Olivia Zhang, Shu‐Dong Yuen, Hiu Fung Shirasawa, Senji Kwok, Hang Fai J Cell Mol Med Original Articles Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser extent in KRAS wild‐type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E‐cadherin in KRAS mutant cells. In human CRC specimens, a high‐level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E‐cadherin expression. Furthermore, we have found that 15 genes were co‐upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer. John Wiley and Sons Inc. 2018-05-30 2018-09 /pmc/articles/PMC6111822/ /pubmed/29851214 http://dx.doi.org/10.1111/jcmm.13686 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wei, Ran
Wong, Janet Pik Ching
Lyu, Peng
Xi, Xinping
Tong, Olivia
Zhang, Shu‐Dong
Yuen, Hiu Fung
Shirasawa, Senji
Kwok, Hang Fai
In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title_full In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title_fullStr In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title_full_unstemmed In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title_short In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer
title_sort in vitro and clinical data analysis of osteopontin as a prognostic indicator in colorectal cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111822/
https://www.ncbi.nlm.nih.gov/pubmed/29851214
http://dx.doi.org/10.1111/jcmm.13686
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