CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_D2A0A84F4163
Type
Article: article from journal or magazin.
Collection
Publications
Title
CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma.
Journal
PLoS One
Author(s)
Dziunycz P.J., Neu J., Lefort K., Djerbi N., Freiberger S.N., Iotzova-Weiss G., French L.E., Dotto G.P., Hofbauer G.F.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
4
Pages
e0173000
Language
english
Abstract
Squamous cell carcinoma of the skin (SCC) represents one of the most common cancers in the general population and is associated with a substantial risk of metastasis. Previous work uncovered the functional role of CYFIP1 in epithelial tumors as an invasion inhibitor. It was down-regulated in some cancers and correlated with the metastatic properties of these malignant cells. We investigated its role and expression mechanisms in SCC. We analyzed the expression of CYFIP1 in patient derived SCC, primary keratinocytes and SCC cell lines, and correlated it to the differentiation and NOTCH1 levels. We analyzed the effects of Notch1 manipulation on CYFIP1 expression and confirmed the biding of Notch1 to the CYFIP1 promoter. CYFIP1 expression was down-regulated in SCC and correlated inversely with histological differentiation of tumors. As keratinocyte differentiation depends on Notch1 signaling, we investigated the influence of Notch1 on CYFIP1 expression. CYFIP1 mRNA was highly increased in human Notch1-overexpressing keratinocytes. Further manipulation of the Notch1 pathway in keratinocytes impacted CYFIP1 levels and chromatin immunoprecipitation assay confirmed the direct binding of Notch1 to the CYFIP1 promoter. CYFIP1 may be a link between loss of differentiation and invasive potential in malignant keratinocytes of cutaneous squamous cell carcinoma.

Keywords
Adaptor Proteins, Signal Transducing/antagonists & inhibitors, Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Carcinoma, Squamous Cell/genetics, Carcinoma, Squamous Cell/metabolism, Carcinoma, Squamous Cell/physiopathology, Cell Differentiation, Cell Line, Cell Movement/drug effects, Chromatin Immunoprecipitation, Down-Regulation, Humans, Keratinocytes/cytology, Keratinocytes/metabolism, Promoter Regions, Genetic, Protein Binding, RNA Interference, RNA, Small Interfering/metabolism, Receptor, Notch1/metabolism, Signal Transduction/drug effects, Skin Neoplasms/genetics, Skin Neoplasms/metabolism, Skin Neoplasms/physiopathology, Tamoxifen/pharmacology, Transcription Factor HES-1/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2017 19:36
Last modification date
20/08/2019 15:52
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