| First Author | Leung WH | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 12 | Pages | 2675-92 |
| PubMed ID | 24190430 | Mgi Jnum | J:207689 |
| Mgi Id | MGI:5559386 | Doi | 10.1084/jem.20122292 |
| Citation | Leung WH, et al. (2013) Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRgamma activation. J Exp Med 210(12):2675-92 |
| abstractText | 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 up-regulate 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 up-regulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its antitumor effects are independent of the mineralocorticoid receptor pathway. By screening the human nuclear hormone receptor siRNA library, we identified retinoid X receptor gamma (RXRgamma) instead as being indispensable for the antitumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXRgamma agonists with minimal side effects for colon cancer prevention and therapy. |
