| Autor: |
Bo’ang Han, Zhen Sun, Tingting Yu, Yu Wang, Lun Kuang, Tianyuan Li, Jing Cai, Qing Cao, Yuan Xu, Binbin Gao, Steven Y. Cheng, Shen Yue, Chen Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell Death Discovery, Vol 7, Iss 1, Pp 1-15 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-021-00484-2 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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