Orphan receptors in prostate cancer

AbstractBackgroundThe identification of new cellular receptors has been increasing rapidly. A receptor is called “orphan” if an endogenous ligand has not been identified yet.MethodsHere we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown.ResultsThe orphan receptors are divided into two major families. The first group includes G protein‐coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110, and GPCR‐X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis.The other major subset of orphan receptors are nuclear receptors. Receptor‐related orphan receptor α (RORα) inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has protumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen‐related receptor ERRγ can inhibit tumor growth but ERRα is protumorigenic. Dax1 and short heterodimeric partner are also inhibitory in prostate cancer.ConclusionThere is a “zoo” of relatively underappreciated orphan receptors that play key roles in prostate cancer.