Targeting truncated RXRα for cancer therapy  

作　　者：Xiaokun Zhang Hu Zhou Ying Su 

机构地区：[1]School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China [2]Sanford Burnham Prebys Medical Discovery Institute, Cancer Center, La Jolla, CA 92037, USA

出　　处：《Acta Biochimica et Biophysica Sinica》2016年第1期49-59,共11页生物化学与生物物理学报（英文版）

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

关 键 词：tRXRα RXRα modulators nongenomic action INFLAMMATION PI3K 

分 类 号：Q74[生物学—分子生物学] TQ174.759[化学工程—陶瓷工业]