Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXR-gamma activation

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: David Finkelstein 

PROVIDER: E-GEOD-50010 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress