Silencing of ASC in Cutaneous Squamous Cell Carcinoma.

Details

Ressource 1Download: journal.pone.0164742.PDF (1392.14 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_AA7773E8C3BF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Silencing of ASC in Cutaneous Squamous Cell Carcinoma.
Journal
PLoS One
Author(s)
Meier K., Drexler S.K., Eberle F.C., Lefort K., Yazdi A.S.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
11
Number
10
Pages
e0164742
Language
english
Abstract
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC. While ASC expression does not correlate with metastatic potential, it correlates with the degree of dedifferentiation. Using methylation specific PCR we were able to demonstrate ASC silencing by promotor specific methylation and impaired inflammasome function in methylated cell lines, linking epigenetic modifications to innate immune activation in keratinocytes. Interestingly, upon ASC restoration by treatment with demethylating agents, we were able to restore AIM2 and NLRP3 activation. In summary, loss of ASC driven tumor development is counterbalanced in the identical cell by the inhibition of pro-tumorigenic inflammation in the tumor cell itself.

Pubmed
Web of science
Open Access
Yes
Create date
01/11/2016 19:20
Last modification date
20/08/2019 15:14
Usage data