AMPK promotes SPOP-mediated NANOG degradation to regulate prostate cancer cell stemness Journal Article

Authors: Wang, X.; Jin, J.; Wan, F.; Zhao, L.; Chu, H.; Chen, C.; Liao, G.; Liu, J.; Yu, Y.; Teng, H.; Fang, L.; Jiang, C.; Pan, W.; Xie, X.; Li, J.; Lu, X.; Jiang, X.; Ge, X.; Ye, D.; Wang, P.
Article Title: AMPK promotes SPOP-mediated NANOG degradation to regulate prostate cancer cell stemness
Abstract: 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, SPOP-mediated 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 stemness controlled by phosphorylation-mediated NANOG stability, which helps to identify novel drug targets and improve therapeutic strategy for PCa. © 2018 Elsevier Inc.
Keywords: controlled study; human tissue; protein expression; protein phosphorylation; unclassified drug; gene mutation; human cell; cancer growth; nonhuman; animal cell; mouse; animal tissue; benzyloxycarbonylleucylleucylleucinal; embryonic stem cell; protein degradation; protein protein interaction; animal experiment; animal model; protein stability; cell differentiation; carcinogenesis; prostate cancer; ubiquitination; amino terminal sequence; cancer stem cell; mutation rate; ubiquitin protein ligase e3; transcription factor nanog; hydroxymethylglutaryl coenzyme a reductase kinase; nanog; cancer prognosis; human; male; priority journal; article; spop; ampk-braf axis; prostate cancer stem cell; 5 amino 4 imidazolecarboxamide riboside; pevonedistat; speckle type poz protein; ampk signaling
Journal Title: Developmental Cell
Volume: 48
Issue: 3
ISSN: 1534-5807
Publisher: Cell Press  
Date Published: 2019-02-11
Start Page: 345
End Page: 360.e7
Language: English
DOI: 10.1016/j.devcel.2018.11.033
PUBMED: 30595535
PROVIDER: scopus
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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MSK Authors
  1. Xuejun Jiang
    79 Jiang