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| Status |
Public on Oct 22, 2013 |
| Title |
Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXR-gamma activation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can upregulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also upregulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its anti-tumor effects are independent of the mineralocorticoid receptor pathway. Instead, by screening the human nuclear hormone receptor siRNA library, we identify retinoid X receptor gamma (RXR gamma) as being indispensable for the anti-tumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXR gamma-agonists with minimal side effects for colon cancer prevention and therapy.
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| Overall design |
Two replicates of two cell types with and without drug
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| |
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| Contributor(s) |
Leung W, Vong QP, Lin W, Janke L, Chen T, Leung W |
| Citation(s) |
24190430 |
| Submission date |
Aug 20, 2013 |
| Last update date |
Apr 20, 2018 |
| Contact name |
David Finkelstein |
| E-mail(s) |
david.finkelstein@stjude.org
|
| Phone |
9014953931
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Computational Biology
|
| Street address |
332 N. Lauderdale St.
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13158 |
[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA215809 |
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