Down-regulation of Filamin Ainteracting protein 1-like is associated with promoter methylation and an invasive phenotype in breast, colon, lung and pancreatic cancers

Mijung Kwon, Soo Jin Lee, Srilakshmi Reddy, Yevangelina Rybak, Asha Adem, Steven K. Libutti

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 downregulation 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.

Original languageEnglish (US)
Article numbere82620
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 5 2013

Fingerprint

filamin
Filamins
pancreatic neoplasms
Methylation
lung neoplasms
colorectal neoplasms
Pancreatic Neoplasms
methylation
breast neoplasms
Colonic Neoplasms
Lung Neoplasms
Down-Regulation
promoter regions
Breast Neoplasms
Phenotype
phenotype
Proteins
proteins
ovarian neoplasms
Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

In: PLoS One, Vol. 8, No. 12, e82620, 05.12.2013.

Research output: Contribution to journalArticle

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. In: PLoS One. 2013 ; Vol. 8, No. 12.
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abstract = "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 downregulation 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.",
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