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ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system. A disintegrin and metallopeptidase with thrombospondin motif (ADAMTS) has been identified as a secreted metalloproteinase that participates in the inhibition of tumor cell growth and inva...

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Autores principales: Zhao, Xuetao, Yang, Congrong, Wu, Jianhua, Nan, Yuemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214590/
https://www.ncbi.nlm.nih.gov/pubmed/30464505
http://dx.doi.org/10.2147/OTT.S173360
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author Zhao, Xuetao
Yang, Congrong
Wu, Jianhua
Nan, Yuemin
author_facet Zhao, Xuetao
Yang, Congrong
Wu, Jianhua
Nan, Yuemin
author_sort Zhao, Xuetao
collection PubMed
description INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system. A disintegrin and metallopeptidase with thrombospondin motif (ADAMTS) has been identified as a secreted metalloproteinase that participates in the inhibition of tumor cell growth and invasion. The aims of the present study were to investigate the clinical significance of ADAMTS8 in patients with HCC and to determine the effect of ADAMTS8 on HCC cell biological activity in vitro and in vivo. METHODS: The tumor tissues and matched adjacent non-tumor tissues were collected from 61 patients with HCC, and ADAMTS8 expression was detected with immunohistochemistry. Flow cytometry and MTT assays were used to assess cell apoptosis and cell viability, respectively, and ERK, p-ERK, Stat3, p-Stat3, Akt, and p-Akt protein expressions were measured by Western blot. RESULTS: The results showed that ADAMTS8 expression was significantly lower in HCC tissues than that in adjacent non-tumor tissues. Moreover, ADAMTS8 expression was inversely associated with clinical stages and metastasis in patients with HCC. Furthermore, we found that transfection with exogenous ADAMTS8 inhibited proliferation and migration and induced apoptosis in HepG2 cells. In the in vivo study, tumor growth of upregulated HepG2 cells in nude mice was significantly slower. Moreover, decreased ERK activity was detected after transfection with ADAMTS8. CONCLUSION: These results indicate that low ADAMTS8 expression is a predictor of a poor prognosis in patients with HCC and that ADAMTS8 plays an important role in regulating HCC growth, invasion, and apoptosis by modulating the ERK signaling pathway. ADAMTS8 maybe a new target in HCC treatment.
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spelling pubmed-62145902018-11-21 ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma Zhao, Xuetao Yang, Congrong Wu, Jianhua Nan, Yuemin Onco Targets Ther Original Research INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system. A disintegrin and metallopeptidase with thrombospondin motif (ADAMTS) has been identified as a secreted metalloproteinase that participates in the inhibition of tumor cell growth and invasion. The aims of the present study were to investigate the clinical significance of ADAMTS8 in patients with HCC and to determine the effect of ADAMTS8 on HCC cell biological activity in vitro and in vivo. METHODS: The tumor tissues and matched adjacent non-tumor tissues were collected from 61 patients with HCC, and ADAMTS8 expression was detected with immunohistochemistry. Flow cytometry and MTT assays were used to assess cell apoptosis and cell viability, respectively, and ERK, p-ERK, Stat3, p-Stat3, Akt, and p-Akt protein expressions were measured by Western blot. RESULTS: The results showed that ADAMTS8 expression was significantly lower in HCC tissues than that in adjacent non-tumor tissues. Moreover, ADAMTS8 expression was inversely associated with clinical stages and metastasis in patients with HCC. Furthermore, we found that transfection with exogenous ADAMTS8 inhibited proliferation and migration and induced apoptosis in HepG2 cells. In the in vivo study, tumor growth of upregulated HepG2 cells in nude mice was significantly slower. Moreover, decreased ERK activity was detected after transfection with ADAMTS8. CONCLUSION: These results indicate that low ADAMTS8 expression is a predictor of a poor prognosis in patients with HCC and that ADAMTS8 plays an important role in regulating HCC growth, invasion, and apoptosis by modulating the ERK signaling pathway. ADAMTS8 maybe a new target in HCC treatment. Dove Medical Press 2018-10-29 /pmc/articles/PMC6214590/ /pubmed/30464505 http://dx.doi.org/10.2147/OTT.S173360 Text en © 2018 Zhao et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhao, Xuetao
Yang, Congrong
Wu, Jianhua
Nan, Yuemin
ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title_full ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title_fullStr ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title_full_unstemmed ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title_short ADAMTS8 targets ERK to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
title_sort adamts8 targets erk to suppress cell proliferation, invasion, and metastasis of hepatocellular carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214590/
https://www.ncbi.nlm.nih.gov/pubmed/30464505
http://dx.doi.org/10.2147/OTT.S173360
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