NANOG is an essential transcriptional factor for the maintenance of embryonic stem cells (ESCs) and cancer stem cells (CSCs) in prostate cancer (PCa). However, the regulation mechanism of NANOG protein stability in cancer progression is still elusive. Here, we report that NANOG is degraded by SPOP, a frequently mutated tumor suppressor of PCa. Cancer -associated mutations of SPOP or the mutation of NANOG at S68Y abrogates the SPOP-mediated NANOG degradation, leading to elevated PCa cancer stemness and poor prognosis. In addition, SPOPmediated NANOG degradation is controlled by the AMPK-BRAF signal axis through the phosphorylation of NANOG at Ser68, which blocked the interaction between SPOP and NANOG. Thus, our study provides a regulation mechanism of PCa sternness controlled by phosphorylation-mediated NANOG stability, which helps to identify novel drug targets and improve therapeutic strategy for PCa.
[1]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr Canc, Shanghai 200072, Peoples R China;
[2]Fudan Univ, Shanghai Canc Ctr, Dept Urol, Shanghai 200032, Peoples R China;
[3]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China;
[4]Tongji Univ, Sch Med, Shanghai Putuo Peoples Hosp, Shanghai 200060, Peoples R China;
[5]East China Normal Univ, Inst Biomed Sci, Shanghai 200241, Peoples R China;
[6]East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China;
[7]Tongji Univ, Sch Med, Dept Clin Med, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China;
[8]Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
[9]Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA
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