SPOP-PTEN-SUFU axis promotes progression of clear cell renal cell carcinoma via activating SHH and WNT pathway.
SPOP-PTEN-SUFU axis promotes progression of clear cell renal cell carcinoma via activating SHH and WNT pathway.
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SPOP-PTEN-SUFU轴通过激活SHH和WNT通路促进透明细胞肾细胞癌的进展
DOI：
10.1038/s41420-021-00484-2
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发表时间：
2021-05-21
影响因子：
7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Han B;Sun Z;Yu T;Wang Y;Kuang L;Li T;Cai J;Cao Q;Xu Y;Gao B;Cheng SY;Yue S;Liu C
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.
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影响因子：
5.6
作者：
Kruck S;Eyrich C;Scharpf M;Sievert KD;Fend F;Stenzl A;Bedke J
通讯作者：
Bedke J
影响因子：
11.8
作者：
Jiang J;Hui CC
通讯作者：
Hui CC
影响因子：
8
作者：
Li, C.;Ao, J.;Fu, J.;Lee, D-F;Xu, J.;Lonard, D.;O'Malley, B. W.
通讯作者：
O'Malley, B. W.
影响因子：
2.9
作者：
Kotulak-Chrzaszcz, Anna;Klacz, Jakub;Wierzbicki, Piotr M.
通讯作者：
Wierzbicki, Piotr M.
影响因子：
37.3
作者：
Dormoy V;Danilin S;Lindner V;Thomas L;Rothhut S;Coquard C;Helwig JJ;Jacqmin D;Lang H;Massfelder T
通讯作者：
Massfelder T