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| Status |
Public on Jan 01, 2017 |
| Title |
CD86 regulates a pro-survival signal in myeloma cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
While multiple myeloma patient prognosis has improved over the past decade, research towards discovery of new therapeutic avenues is important, and could lead to a cure for this chronic plasma cell malignancy. Data analysis from a myeloma patient database shows that the CD28-CD86 signaling module may provide a survival advantage in myeloma cells that negatively impacts patient outcome. Here we show that blocking the CD28-CD86 pathway, by silencing or with CTLA-4-Ig, leads to myeloma cell death. Blockade of this pathway leads to downregulation of nutrient transporters, integrins, and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical "ligand" in this pathway, is mediating a pro-survival signal via the cytosolic domain that has not been previously described. These findings indicate that blockade of this pathway is a promising therapeutic avenue for myeloma, as it leads to modulation of different processes important in cell viability.
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| Overall design |
The myeloma cell lines MM.1s, RPMI8226, KMS18, and RPMI8226 that overexpresses the anti-apoptotic protein Mcl1 were transfected with short hairpin RNAs targeting CD28, CD86, Gapdh (control), or empty vector (pLK0.1) control and gene expression analysis was performed by RNA-seq.
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| |
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| Contributor(s) |
Gavile CM, Barwick BG, Lawrence BH |
| Citation(s) |
29296880 |
| |
| Submission date |
Nov 03, 2016 |
| Last update date |
Mar 28, 2022 |
| Contact name |
Benjamin G Barwick |
| E-mail(s) |
benjamin.barwick@emory.edu
|
| Phone |
(404) 285-2964
|
| Organization name |
Emory University
|
| Department |
Hematology and Medical Oncology
|
| Lab |
Barwick Lab
|
| Street address |
1365 Clifton Rd. NE WCI-C 4th Floor Benches 36-37
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (16)
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| Relations |
| BioProject |
PRJNA352410 |
| SRA |
SRP092559 |
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