title: USP8: a novel therapeutic target for Cushing's disease.
abstract: Cushing's disease (CD), caused by an adrenocorticotropin-secreting pituitary adenoma, leads to hypercortisolemia and causes serious morbidity and increased mortality when suboptimally treated. Currently, the genetic events have rarely been reported in this disease. Recently, the recurrent activating mutations in the gene encoding ubiquitin-specific protease 8 (USP8) in CD have been independently reported by two teams. These hotspot mutations sustain epidermal growth factor receptor (EGFR) signaling and expand the pathogenic role of USP8 in corticotroph adenoma. This review summarizes current knowledge of USP8 and its substrate EGFR in cancer therapy and possible application of them in CD.
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jian
authors.affiliation: Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. blg11118@rjh.com.cn.
authors.forename: Liuguan
authors.initials: L
authors.lastname: Bian
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai, 200025, China. aibuxuyaoliyou@sjtu.edu.cn.|Department of Neurosurgery, Ruijin Hospital, Luwan Branch, Shanghai Jiao Tong University School of Medicine, No. 149, South Chongqing Road, Shanghai, 200025, China. aibuxuyaoliyou@sjtu.edu.cn.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Sun
mesh_terms: D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy* / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C512478:EGFR protein, human; D066246:ErbB Receptors; D010450:Endopeptidases; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Cushing’s disease; EGFR; Medical therapy; USP8