Cargando…
FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer
BACKGROUND: Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. METHODS: Apolipoprotein (ApoE) knock-out mice was used to analyze t...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819228/ https://www.ncbi.nlm.nih.gov/pubmed/29458390 http://dx.doi.org/10.1186/s13046-018-0696-4 |
_version_ | 1783301170872188928 |
---|---|
author | Lai, Huiling Zhao, Xuejiao Qin, Yu Ding, Yi Chen, Ruqi Li, Guannan Labrie, Marilyne Ding, Zhiyong Zhou, Jianfeng Hu, Junbo Ma, Ding Fang, Yong Gao, Qinglei |
author_facet | Lai, Huiling Zhao, Xuejiao Qin, Yu Ding, Yi Chen, Ruqi Li, Guannan Labrie, Marilyne Ding, Zhiyong Zhou, Jianfeng Hu, Junbo Ma, Ding Fang, Yong Gao, Qinglei |
author_sort | Lai, Huiling |
collection | PubMed |
description | BACKGROUND: Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. METHODS: Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian cancer cells. RESULTS: ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian cancer progression. CONCLUSIONS: These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new anticancer therapeutic combinations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0696-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5819228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58192282018-02-21 FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer Lai, Huiling Zhao, Xuejiao Qin, Yu Ding, Yi Chen, Ruqi Li, Guannan Labrie, Marilyne Ding, Zhiyong Zhou, Jianfeng Hu, Junbo Ma, Ding Fang, Yong Gao, Qinglei J Exp Clin Cancer Res Research BACKGROUND: Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. METHODS: Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian cancer cells. RESULTS: ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian cancer progression. CONCLUSIONS: These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new anticancer therapeutic combinations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0696-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819228/ /pubmed/29458390 http://dx.doi.org/10.1186/s13046-018-0696-4 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 Lai, Huiling Zhao, Xuejiao Qin, Yu Ding, Yi Chen, Ruqi Li, Guannan Labrie, Marilyne Ding, Zhiyong Zhou, Jianfeng Hu, Junbo Ma, Ding Fang, Yong Gao, Qinglei FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title | FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title_full | FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title_fullStr | FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title_full_unstemmed | FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title_short | FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer |
title_sort | fak-erk activation in cell/matrix adhesion induced by the loss of apolipoprotein e stimulates the malignant progression of ovarian cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819228/ https://www.ncbi.nlm.nih.gov/pubmed/29458390 http://dx.doi.org/10.1186/s13046-018-0696-4 |
work_keys_str_mv | AT laihuiling fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT zhaoxuejiao fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT qinyu fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT dingyi fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT chenruqi fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT liguannan fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT labriemarilyne fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT dingzhiyong fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT zhoujianfeng fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT hujunbo fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT mading fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT fangyong fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer AT gaoqinglei fakerkactivationincellmatrixadhesioninducedbythelossofapolipoproteinestimulatesthemalignantprogressionofovariancancer |