Phosphorylation of FOXP3 by LCK downregulates MMP9 expression and represses cell invasion = FOXP3의 인산화에 의한 MMP의 발현 및 세포 전이 억제

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Title
Phosphorylation of FOXP3 by LCK downregulates MMP9 expression and represses cell invasion = FOXP3의 인산화에 의한 MMP의 발현 및 세포 전이 억제
Author(s)
K Nakahira; A Morita; Nam-Soon Kim; I Yanagihara
Bibliographic Citation
PLoS One, vol. 8, no. 10, pp. e77099-e77099
Publication Year
2013
Abstract
Forkhead Box P3 (FOXP3) is a member of the forkhead/winged helix family of the transcription factors and plays an important role not only as a master gene in T-regulatory cells, but also as a tumor suppressor. In this study, we identified lymphocyte-specific protein tyrosine kinase (LCK), which correlates with cancer malignancy, as a binding partner of FOXP3. FOXP3 downregulated LCK-induced MMP9, SKP2, and VEGF-A expression. We observed that LCK phosphorylated Tyr-342 of FOXP3 by immunoprecipitation and in vitro kinase assay, and the replacement of Tyr-342 with phenylalanine (Y342F) abolished the ability to suppress MMP9 expression. Although FOXP3 decreased the invasive ability induced by LCK in MCF-7 cells, Y342F mutation in FOXP3 diminished this suppressive effect. Thus we demonstrate for the first time that LCK upregulates FOXP3 by tyrosine phosphorylation, resulting in decreased MMP9, SKP2, and VEGF-A expression, and suppressed cellular invasion. We consider that further clarification of transcriptional mechanism of FOXP3 may facilitate the development of novel therapeutic approaches to suppress cancer malignancy.
ISSN
1932-6203
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pone.0077099
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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