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C-FLIP promotes the motility of cancer cells by activating FAK and ERK, and increasing MMP-9 expression.
Mol Cells. 2008 Apr 30; 25(2):184-95.MC

Abstract

We examined the role of c-FLIP in the motility of HeLa cells. A small interfering RNA (siRNA) directed against c-FLIP inhibited the adhesion and motility of the cells without affecting their growth rate. The long form of c-FLIP (c-FLIPL), but not the short form (c-FLIPS), enhanced adhesion and motility. Downregulation of c-FLIPL with siRNA decreased phosphorylation of FAK and ERK, while overexpression of c-FLIPL increased their phosphorylation. Overexpression of FAK activated ERK, and enhanced the motility of HeLa cells. FRNK, an inhibitory fragment of FAK, inhibited ERK and decreased motility. Inhibition of ERK also significantly suppressed c-FLIPL-promoted motility. Inhibition of ROCK by Y27632 suppressed the c-FLIPL-promoted motility by reducing phosphorylation of FAK and ERK. Overexpression of c-FLIPL increased the expression and secretion of MMP-9, and inhibition of MMP-9 by Ilomastat reduced c-FLIPL- promoted cell motility. A caspase-like domain (amino acids 222-376) was found to be necessary for the c-FLIPL-promoted cell motility. We conclude that c-FLIPL promotes the motility of HeLa cells by activating FAK and ERK, and increasing MMP-9 expression.

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Authors+Show Affiliations

Park D
School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Shim E
No affiliation info available
Kim Y
No affiliation info available
Kim YM
No affiliation info available
Lee H
No affiliation info available
Choe J
No affiliation info available
Kang D
No affiliation info available
Lee YS
No affiliation info available
Jeoung D
No affiliation info available

MeSH

CASP8 and FADD-Like Apoptosis Regulating ProteinCell AdhesionCell MovementCell ProliferationEnzyme ActivationExtracellular Matrix ProteinsExtracellular Signal-Regulated MAP KinasesFocal Adhesion Protein-Tyrosine KinasesHeLa CellsHumansMatrix Metalloproteinase 9Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NeoplasmsPhosphorylationProtein IsoformsProtein Kinase InhibitorsProtein Structure, TertiaryRNA, Small InterferingTransfectionrho-Associated Kinases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18414015

Citation

Park, Deokbum, et al. "C-FLIP Promotes the Motility of Cancer Cells By Activating FAK and ERK, and Increasing MMP-9 Expression." Molecules and Cells, vol. 25, no. 2, 2008, pp. 184-95.
Park D, Shim E, Kim Y, et al. C-FLIP promotes the motility of cancer cells by activating FAK and ERK, and increasing MMP-9 expression. Mol Cells. 2008;25(2):184-95.
Park, D., Shim, E., Kim, Y., Kim, Y. M., Lee, H., Choe, J., Kang, D., Lee, Y. S., & Jeoung, D. (2008). C-FLIP promotes the motility of cancer cells by activating FAK and ERK, and increasing MMP-9 expression. Molecules and Cells, 25(2), 184-95.
Park D, et al. C-FLIP Promotes the Motility of Cancer Cells By Activating FAK and ERK, and Increasing MMP-9 Expression. Mol Cells. 2008 Apr 30;25(2):184-95. PubMed PMID: 18414015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C-FLIP promotes the motility of cancer cells by activating FAK and ERK, and increasing MMP-9 expression. AU - Park,Deokbum, AU - Shim,Eunsook, AU - Kim,Youngmi, AU - Kim,Young Myeong, AU - Lee,Hansoo, AU - Choe,Jongseon, AU - Kang,Dongmin, AU - Lee,Yun-Sil, AU - Jeoung,Dooil, Y1 - 2008/03/28/ PY - 2008/4/17/pubmed PY - 2008/8/5/medline PY - 2008/4/17/entrez SP - 184 EP - 95 JF - Molecules and cells JO - Mol Cells VL - 25 IS - 2 N2 - We examined the role of c-FLIP in the motility of HeLa cells. A small interfering RNA (siRNA) directed against c-FLIP inhibited the adhesion and motility of the cells without affecting their growth rate. The long form of c-FLIP (c-FLIPL), but not the short form (c-FLIPS), enhanced adhesion and motility. Downregulation of c-FLIPL with siRNA decreased phosphorylation of FAK and ERK, while overexpression of c-FLIPL increased their phosphorylation. Overexpression of FAK activated ERK, and enhanced the motility of HeLa cells. FRNK, an inhibitory fragment of FAK, inhibited ERK and decreased motility. Inhibition of ERK also significantly suppressed c-FLIPL-promoted motility. Inhibition of ROCK by Y27632 suppressed the c-FLIPL-promoted motility by reducing phosphorylation of FAK and ERK. Overexpression of c-FLIPL increased the expression and secretion of MMP-9, and inhibition of MMP-9 by Ilomastat reduced c-FLIPL- promoted cell motility. A caspase-like domain (amino acids 222-376) was found to be necessary for the c-FLIPL-promoted cell motility. We conclude that c-FLIPL promotes the motility of HeLa cells by activating FAK and ERK, and increasing MMP-9 expression. SN - 1016-8478 UR - https://www.unboundmedicine.com/medline/citation/18414015/C_FLIP_promotes_the_motility_of_cancer_cells_by_activating_FAK_and_ERK_and_increasing_MMP_9_expression_ L2 - http://www.molcells.org/journal/view.html?year=2008&volume=25&number=2&spage=184 DB - PRIME DP - Unbound Medicine ER -