Targeting truncated RXR? for cancer therapy.

ABSTRACT: Retinoid X receptor-alpha (RXR?), a unique member of the nuclear receptor superfamily, is a well-established drug target, representing one of the most important targets for pharmacologic interventions and therapeutic applications for cancer. However, how RXR? regulates cancer cell growth and how RXR? modulators suppress tumorigenesis are poorly understood. Altered expression and aberrant function of RXR? are implicated in the development of cancer. Previously, several studies had demonstrated the presence of N-terminally truncated RXR? (tRXR?) proteins resulted from limited proteolysis of RXR? in tumor cells. Recently, we discovered that overexpression of tRXR? can promote tumor growth by interacting with tumor necrosis factor-alpha-induced phosphoinositide 3-kinase and NF-?B signal transduction pathways. We also identified nonsteroidal anti-inflammatory drug Sulindac and analogs as effective inhibitors of tRXR? activities via a unique binding mechanism. This review discusses the emerging roles of tRXR? and modulators in the regulation of cancer cell survival and death as well as inflammation and our recent understanding of tRXR? regulation by targeting the alternate binding sites on its surface.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC4689158 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature