Cargando…
Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway
Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the un...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783154/ https://www.ncbi.nlm.nih.gov/pubmed/29403285 http://dx.doi.org/10.2147/OTT.S155511 |
_version_ | 1783295244204244992 |
---|---|
author | Daya, Minerva Loilome, Watcharin Techasen, Anchalee Thanee, Malinee Sa-Ngiamwibool, Prakasit Titapun, Attapol Yongvanit, Puangrat Namwat, Nisana |
author_facet | Daya, Minerva Loilome, Watcharin Techasen, Anchalee Thanee, Malinee Sa-Ngiamwibool, Prakasit Titapun, Attapol Yongvanit, Puangrat Namwat, Nisana |
author_sort | Daya, Minerva |
collection | PubMed |
description | Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K) and phosphorylated Akt (pAkt) proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial–mesenchymal transition (EMT) revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In conclusion, our findings imply that PGRN modulates cell proliferation by dysregulating the G1 phase, inhibiting apoptosis, and that it plays a role in the EMT affecting CCA cell motility, possibly via the PI3K/pAkt pathway. |
format | Online Article Text |
id | pubmed-5783154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57831542018-02-05 Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway Daya, Minerva Loilome, Watcharin Techasen, Anchalee Thanee, Malinee Sa-Ngiamwibool, Prakasit Titapun, Attapol Yongvanit, Puangrat Namwat, Nisana Onco Targets Ther Original Research Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K) and phosphorylated Akt (pAkt) proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial–mesenchymal transition (EMT) revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In conclusion, our findings imply that PGRN modulates cell proliferation by dysregulating the G1 phase, inhibiting apoptosis, and that it plays a role in the EMT affecting CCA cell motility, possibly via the PI3K/pAkt pathway. Dove Medical Press 2018-01-18 /pmc/articles/PMC5783154/ /pubmed/29403285 http://dx.doi.org/10.2147/OTT.S155511 Text en © 2018 Daya 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 Daya, Minerva Loilome, Watcharin Techasen, Anchalee Thanee, Malinee Sa-Ngiamwibool, Prakasit Titapun, Attapol Yongvanit, Puangrat Namwat, Nisana Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title | Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title_full | Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title_fullStr | Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title_full_unstemmed | Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title_short | Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway |
title_sort | progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the pi3k/pakt pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783154/ https://www.ncbi.nlm.nih.gov/pubmed/29403285 http://dx.doi.org/10.2147/OTT.S155511 |
work_keys_str_mv | AT dayaminerva progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT loilomewatcharin progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT techasenanchalee progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT thaneemalinee progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT sangiamwiboolprakasit progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT titapunattapol progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT yongvanitpuangrat progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway AT namwatnisana progranulinmodulatescholangiocarcinomacellproliferationapoptosisandmotilityviathepi3kpaktpathway |