Cargando…

Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway

Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development a...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Yingying, Yang, Ling, Yang, Yujie, Han, Yanyan, Wang, Yongbo, Liu, Wen, Zuo, Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082394/
https://www.ncbi.nlm.nih.gov/pubmed/27374312
http://dx.doi.org/10.1111/jcmm.12905
_version_ 1782463049157836800
author Hu, Yingying
Yang, Ling
Yang, Yujie
Han, Yanyan
Wang, Yongbo
Liu, Wen
Zuo, Ji
author_facet Hu, Yingying
Yang, Ling
Yang, Yujie
Han, Yanyan
Wang, Yongbo
Liu, Wen
Zuo, Ji
author_sort Hu, Yingying
collection PubMed
description Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development and progression. In this study, lentivirus‐delivered mortalin short hairpin RNA (shRNA) was used to knockdown mortalin expression in A2780 and A2780/cis ovarian cancer cell lines, and lentiviral mortalin‐pLVX‐AcGFP was used to generate mortalin‐overexpressing cell lines. The results demonstrated that decreased mortalin expression reduced ovarian cancer cell proliferation, colony formation, migration and invasion by Cell Counting Kit‐8 assay, colony formation assay, wounding healing assay and Transwell cell invasion assay, respectively. Flow cytometry results suggested that mortalin promotes the G1 transition, leading to faster restoration of a normal cell‐cycle distribution. Cell‐cycle proteins, including C‐myc and Cyclin‐D1, significantly increased, and Cyclin‐B1 remarkably decreased upon mortalin down‐regulation. Western blot analysis showed that mortalin knockdown significantly decreased p‐c‐Raf and phospho‐extracellular–regulated protein kinases (p‐ERK1/2) pathways but not the Jun N‐terminal kinase pathway, whereas mortalin overexpression had the opposite effect. Taken together, these results indicate that mortalin is an oncogenic factor, and mitogen‐activated protein kinase‐ERK signalling pathway activation by mortalin may contribute to ovarian cancer development and progression.
format Online
Article
Text
id pubmed-5082394
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-50823942016-11-01 Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway Hu, Yingying Yang, Ling Yang, Yujie Han, Yanyan Wang, Yongbo Liu, Wen Zuo, Ji J Cell Mol Med Original Articles Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development and progression. In this study, lentivirus‐delivered mortalin short hairpin RNA (shRNA) was used to knockdown mortalin expression in A2780 and A2780/cis ovarian cancer cell lines, and lentiviral mortalin‐pLVX‐AcGFP was used to generate mortalin‐overexpressing cell lines. The results demonstrated that decreased mortalin expression reduced ovarian cancer cell proliferation, colony formation, migration and invasion by Cell Counting Kit‐8 assay, colony formation assay, wounding healing assay and Transwell cell invasion assay, respectively. Flow cytometry results suggested that mortalin promotes the G1 transition, leading to faster restoration of a normal cell‐cycle distribution. Cell‐cycle proteins, including C‐myc and Cyclin‐D1, significantly increased, and Cyclin‐B1 remarkably decreased upon mortalin down‐regulation. Western blot analysis showed that mortalin knockdown significantly decreased p‐c‐Raf and phospho‐extracellular–regulated protein kinases (p‐ERK1/2) pathways but not the Jun N‐terminal kinase pathway, whereas mortalin overexpression had the opposite effect. Taken together, these results indicate that mortalin is an oncogenic factor, and mitogen‐activated protein kinase‐ERK signalling pathway activation by mortalin may contribute to ovarian cancer development and progression. John Wiley and Sons Inc. 2016-07-04 2016-11 /pmc/articles/PMC5082394/ /pubmed/27374312 http://dx.doi.org/10.1111/jcmm.12905 Text en © 2016 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 Creative Commons Attribution (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
Hu, Yingying
Yang, Ling
Yang, Yujie
Han, Yanyan
Wang, Yongbo
Liu, Wen
Zuo, Ji
Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title_full Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title_fullStr Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title_full_unstemmed Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title_short Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK–ERK pathway
title_sort oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the mapk–erk pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082394/
https://www.ncbi.nlm.nih.gov/pubmed/27374312
http://dx.doi.org/10.1111/jcmm.12905
work_keys_str_mv AT huyingying oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT yangling oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT yangyujie oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT hanyanyan oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT wangyongbo oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT liuwen oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway
AT zuoji oncogenicroleofmortalincontributestoovariantumorigenesisbyactivatingthemapkerkpathway