Cargando…

Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers

Identifying key mediators of cancer cell invasion and metastasis is critical to the development of more effective cancer therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important inhibitor of cell migration and invasion in ovarian cancer. FILIP1L expression w...

Descripción completa

Detalles Bibliográficos
Autores principales: Kwon, Mijung, Lee, Soo Jin, Reddy, Srilakshmi, Rybak, Yevangelina, Adem, Asha, Libutti, Steven K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855469/
https://www.ncbi.nlm.nih.gov/pubmed/24340050
http://dx.doi.org/10.1371/journal.pone.0082620
_version_ 1782294922292887552
author Kwon, Mijung
Lee, Soo Jin
Reddy, Srilakshmi
Rybak, Yevangelina
Adem, Asha
Libutti, Steven K.
author_facet Kwon, Mijung
Lee, Soo Jin
Reddy, Srilakshmi
Rybak, Yevangelina
Adem, Asha
Libutti, Steven K.
author_sort Kwon, Mijung
collection PubMed
description Identifying key mediators of cancer cell invasion and metastasis is critical to the development of more effective cancer therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important inhibitor of cell migration and invasion in ovarian cancer. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and ovarian cancer specimens. We also demonstrated that DNA methylation in the FILIP1L promoter was a mechanism by which FILIP1L was down-regulated in ovarian cancer. In our present study, we tested this observation in other cancer histologies: breast, colon, lung and pancreatic cancers. Both mRNA and protein expression of FILIP1L were down-regulated in these cancer cells compared with their normal epithelial cells. As in ovarian cancer, DNA methylation is a mechanism by which FILIP1L is down-regulated in these cancer histologies. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in these cancer cells. Further, FILIP1L expression was inversely correlated with the invasive potential of these cancer cells. Re-expression of FILIP1L in FILIP1L-low expressing, highly-invasive cancer cell lines resulted in inhibition of cell invasion. Correspondingly, knockdown of FILIP1L in FILIP1L-high expressing, low-invasive cancer cell lines resulted in increase of cell invasion. Overall, these findings suggest that down-regulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in various cancers. Thus, modulation of FILIP1L expression has the potential to be a target for cancer therapy.
format Online
Article
Text
id pubmed-3855469
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38554692013-12-11 Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers Kwon, Mijung Lee, Soo Jin Reddy, Srilakshmi Rybak, Yevangelina Adem, Asha Libutti, Steven K. PLoS One Research Article Identifying key mediators of cancer cell invasion and metastasis is critical to the development of more effective cancer therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important inhibitor of cell migration and invasion in ovarian cancer. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and ovarian cancer specimens. We also demonstrated that DNA methylation in the FILIP1L promoter was a mechanism by which FILIP1L was down-regulated in ovarian cancer. In our present study, we tested this observation in other cancer histologies: breast, colon, lung and pancreatic cancers. Both mRNA and protein expression of FILIP1L were down-regulated in these cancer cells compared with their normal epithelial cells. As in ovarian cancer, DNA methylation is a mechanism by which FILIP1L is down-regulated in these cancer histologies. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in these cancer cells. Further, FILIP1L expression was inversely correlated with the invasive potential of these cancer cells. Re-expression of FILIP1L in FILIP1L-low expressing, highly-invasive cancer cell lines resulted in inhibition of cell invasion. Correspondingly, knockdown of FILIP1L in FILIP1L-high expressing, low-invasive cancer cell lines resulted in increase of cell invasion. Overall, these findings suggest that down-regulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in various cancers. Thus, modulation of FILIP1L expression has the potential to be a target for cancer therapy. Public Library of Science 2013-12-05 /pmc/articles/PMC3855469/ /pubmed/24340050 http://dx.doi.org/10.1371/journal.pone.0082620 Text en © 2013 Kwon et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kwon, Mijung
Lee, Soo Jin
Reddy, Srilakshmi
Rybak, Yevangelina
Adem, Asha
Libutti, Steven K.
Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title_full Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title_fullStr Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title_full_unstemmed Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title_short Down-Regulation of Filamin Ainteracting protein 1-like Is Associated with Promoter Methylation and an Invasive Phenotype in Breast, Colon, Lung and Pancreatic Cancers
title_sort down-regulation of filamin ainteracting protein 1-like is associated with promoter methylation and an invasive phenotype in breast, colon, lung and pancreatic cancers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855469/
https://www.ncbi.nlm.nih.gov/pubmed/24340050
http://dx.doi.org/10.1371/journal.pone.0082620
work_keys_str_mv AT kwonmijung downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers
AT leesoojin downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers
AT reddysrilakshmi downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers
AT rybakyevangelina downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers
AT ademasha downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers
AT libuttistevenk downregulationoffilaminainteractingprotein1likeisassociatedwithpromotermethylationandaninvasivephenotypeinbreastcolonlungandpancreaticcancers