PMID- 34021128
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210608
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 7
IP  - 1
DP  - 2021 May 21
TI  - SPOP-PTEN-SUFU axis promotes progression of clear cell renal cell carcinoma via 
      activating SHH and WNT pathway.
PG  - 120
LID - 10.1038/s41420-021-00484-2 [doi]
LID - 120
AB  - Although E3 ligase Speckle type BTB/POZ protein (SPOP) promotes tumorigenesis by 
      acting as a key regulatory hub in clear cell renal cell carcinoma (ccRCC), the 
      detailed molecular mechanism remains unclear. Here, we demonstrate that a 
      well-known tumor suppressor, Suppressor of Fused (SUFU), is downregulated by 
      SPOP. Interestingly, this downregulation depends on cullin-3(Cul3)-SPOP E3 
      ligase, but SUFU is not a direct substrate of SPOP. Phosphatase and tensin 
      homolog (PTEN), a ubiquitinated substrate of SPOP, is involved in SPOP-mediated 
      SUFU reduction. Importantly, inhibition of SUFU leads to elevated SHH and WNT 
      signaling, consequently rescuing the reduced proliferation, migration, and 
      invasion abilities of ccRCC cells caused by SPOP-knockdown. Moreover, 
      combinatorial treatment with SHH and WNT inhibitors shows more effective for 
      suppressing ccRCC cell proliferation and aggressiveness. These findings 
      demonstrate that a novel SPOP-PTEN-SUFU axis promotes ccRCC carcinogenesis by 
      activating SHH and WNT pathway, providing a new treatment strategy for ccRCC.
FAU - Han, Bo'ang
AU  - Han B
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
AD  - Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative 
      Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 
      211166, Nanjing, China.
AD  - Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 
      211166, Nanjing, China.
FAU - Sun, Zhen
AU  - Sun Z
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
AD  - Department of Pathology, Affiliated Zhongshan Hospital of Dalian University, 
      116001, Dalian, China.
FAU - Yu, Tingting
AU  - Yu T
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
AD  - Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 
      211166, Nanjing, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
FAU - Kuang, Lun
AU  - Kuang L
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
FAU - Li, Tianyuan
AU  - Li T
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
FAU - Cai, Jing
AU  - Cai J
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
FAU - Cao, Qing
AU  - Cao Q
AD  - College of Medicine, Henan University of Science and Technology, 471023, Luoyang, 
      China.
FAU - Xu, Yuan
AU  - Xu Y
AD  - The First School of Clinical Medicine, Nanjing Medical University, 211166, 
      Nanjing, China.
FAU - Gao, Binbin
AU  - Gao B
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China.
FAU - Cheng, Steven Y
AU  - Cheng SY
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China. sycheng@njmu.edu.cn.
AD  - Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative 
      Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 
      211166, Nanjing, China. sycheng@njmu.edu.cn.
AD  - Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 
      211166, Nanjing, China. sycheng@njmu.edu.cn.
FAU - Yue, Shen
AU  - Yue S
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China. yueshen@njmu.edu.cn.
AD  - Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative 
      Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 
      211166, Nanjing, China. yueshen@njmu.edu.cn.
AD  - Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 
      211166, Nanjing, China. yueshen@njmu.edu.cn.
FAU - Liu, Chen
AU  - Liu C
AUID- ORCID: 0000-0002-7134-4367
AD  - Department of Medical Genetics, Nanjing Medical University, 211166, Nanjing, 
      China. liuchen@njmu.edu.cn.
AD  - Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 
      211166, Nanjing, China. liuchen@njmu.edu.cn.
LA  - eng
GR  - 81702747/National Science Foundation of China | Young Scientists Fund/
GR  - 81602431/National Science Foundation of China | Young Scientists Fund/
GR  - BK20171053/Natural Science Foundation of Jiangsu Province (Jiangsu Provincial 
      Natural Science Foundation)/
GR  - 13480027/Henan University of Science and Technology (HUST)/
GR  - NMUD2019007/Nanjing Medical University (NMU)/
GR  - 81672748/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - 81572720/National Natural Science Foundation of China (National Science 
      Foundation of China)/
PT  - Journal Article
DEP - 20210521
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC8140158
COIS- The authors declare no competing interests.
EDAT- 2021/05/23 06:00
MHDA- 2021/05/23 06:01
PMCR- 2021/05/21
CRDT- 2021/05/22 05:40
PHST- 2020/10/20 00:00 [received]
PHST- 2021/04/19 00:00 [accepted]
PHST- 2021/04/02 00:00 [revised]
PHST- 2021/05/22 05:40 [entrez]
PHST- 2021/05/23 06:00 [pubmed]
PHST- 2021/05/23 06:01 [medline]
PHST- 2021/05/21 00:00 [pmc-release]
AID - 10.1038/s41420-021-00484-2 [pii]
AID - 484 [pii]
AID - 10.1038/s41420-021-00484-2 [doi]
PST - epublish
SO  - Cell Death Discov. 2021 May 21;7(1):120. doi: 10.1038/s41420-021-00484-2.