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Series GSE43878 Query DataSets for GSE43878
Status Public on Mar 13, 2013
Title Control of Autophagic Cell Death by Caspase-10 in Multiple Myeloma
Organism Homo sapiens
Experiment type Expression profiling by array
Summary We performed a loss-of-function, RNA interference screen to define new therapeutic targets in multiple myeloma, a genetically diverse plasma cell malignancy. Unexpectedly, we discovered that all myeloma lines require caspase-10 for survival, irrespective of their genetic abnormalities. The transcription factor IRF4 induces both caspase-10 and its associated protein cFLIPL in myeloma, generating a protease that does not induce apoptosis but rather blocks an autophagy-dependent cell death pathway. Caspase-10 inhibits autophagy by cleaving the BCL2-interacting protein BCLAF1, itself a strong inducer of autophagy that acts by displacing beclin-1 from BCL2. While myeloma cells require a basal level of autophagy for survival, caspase-10 tempers this response to avoid cell death. Drugs that disrupt this vital balance may have therapeutic potential in myeloma.
 
Overall design To generate a gene expression signature of caspase 10 signaling in multiple myeloma, cell lines (SKMM1 n=16, KMS12 n=8 and H929 n=12) were transduced with retroviral vectors expressing either shCasp10-2 or shCasp10-3. Similarly, lymphoma cell lines (OCI-Ly7 n=2 and OCI-Ly19 n=2) were transduced and used as a control. Following puromycin selection, shRNA expression was induced for 24 to 120 hours and gene expression was measured, comparing uninduced (Cy3) to induced (Cy5) cells, using lymphochip microarrays. Biological repeats were performed of H929 and SKMM1 samples.
 
Citation(s) 23541952
Submission date Jan 29, 2013
Last update date Jun 16, 2014
Contact name Louis M. Staudt
E-mail(s) lstaudt@mail.nih.gov
Phone 301-402-1892
Organization name National Cancer Institute
Department Lymphoid Malignancies Branch
Lab Louis M Staudt
Street address 9000 Rockville Pike, Bldg 10, Rm 4N114
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL3278 NCI/Staudt human 15K v13
Samples (40)
GSM1072714 SKMM1 shCasp10-2 - day 4 - repeat 3 - mAdbID:81160
GSM1072715 SKMM1 shCasp10-2 - day 3 - repeat 3 - mAdbID:81161
GSM1072716 SKMM1 shCasp10-2 - day 2 - repeat 3 - mAdbID:81162
Relations
BioProject PRJNA188236

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43878_RAW.tar 53.9 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table
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