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Series GSE113328 Query DataSets for GSE113328
Status Public on Apr 19, 2018
Title Expression data from WT and TNFRSF19 KO HNE-1 cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Genetic susceptibility underlies the pathogenesis of cancer. Through genome-wide association studies, we and others have previously identified a novel susceptibility gene, TNFRSF19, which encodes an orphan member of the TNF receptor superfamily, to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation and NPC development. However, unlike most of TNF receptors, TNFRSF19 is not involved in NF-B activation or associated with TRAF proteins. By affinity purification, we identified TGFβ receptor type-I (TβRI) as a specific binding partner for TNFRSF19. TNFRSF19 binds to the kinase domain of TβRI in the cytoplasm and thereby blocks the Smad2/3 association with TβRI and subsequent signal transduction. Ectopic expression of TNFRSF19 in normal epithelial cells confers resistance to the cell cycle block induced by TGFβ, whereas knockout of TNFRSF19 in NPC cells unleashes a potent TGFβ response characterized by upregulation of Smad2/3 phosphorylation and TGFβ target gene transcription. Furthermore, elevated TNFRSF19 expression correlates with reduced TGFβ activity and poor prognosis in NPC patients. Our data reveal that gain-of-function of TNFRSF19 in NPC represents a mechanism by which tumor cells evade the growth-inhibitory action of TGFβ.
Hierarchical cluster assays of the differentially expressed genes between TNFRSF19 WT and KO single clones of HNE-1 cells.
 
Overall design TNFRSF19 WT and KO single clones of HNE-1 cells were selected for RNA extraction and hybridization on Affymetrix microarrays.
 
Contributor(s) Feng L, Zeng Y
Citation(s) 29735548
Submission date Apr 18, 2018
Last update date Mar 25, 2019
Contact name Lin Feng
E-mail fengl@sysucc.org.cn
Organization name Sun Yat-sen University Cancer Center
Street address 651 Dongfeng East Road
City Guangzhou
ZIP/Postal code 510060
Country China
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (2)
GSM3103302 HNE-1 TNFRSF19 WT
GSM3103303 HNE-1 TNFRSF19 KO
Relations
BioProject PRJNA450824

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE113328_RAW.tar 8.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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