SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.
SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.
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DOI：
10.1016/j.ccr.2014.02.007
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发表时间：
2014-04-14
期刊：
影响因子：
50.3
通讯作者：
White KP
中科院分区：
文献类型：
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作者：
Li G;Ci W;Karmakar S;Chen K;Dhar R;Fan Z;Guo Z;Zhang J;Ke Y;Wang L;Zhuang M;Hu S;Li X;Zhou L;Li X;Calabrese MF;Watson ER;Prasad SM;Rinker-Schaeffer C;Eggener SE;Stricker T;Tian Y;Schulman BA;Liu J;White KP
低氧应激和低氧诱导因子（hif）在多种肿瘤中发挥着重要作用。我们证明编码E3泛素连接酶组分的SPOP是透明细胞肾细胞癌（ccRCC）中hif的直接转录靶点。此外，缺氧导致细胞质中SPOP的积累，这足以诱导肿瘤发生。这种致瘤活性通过多种细胞增殖和凋亡调节因子的泛素化和降解发生，包括肿瘤抑制因子PTEN、ERK磷酸酶、促凋亡分子Daxx和Hedgehog途径转录因子Gli2。敲低SPOP特异性杀死ccRCC细胞，表明它可能是一个有希望的治疗靶点。总之，我们的研究结果表明SPOP是促进ccRCC肿瘤发生的调控中心。
Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the pro-apoptotic molecule Daxx and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.
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影响因子：
4
作者：
Hung, Mien-Chie;Link, Wolfgang
通讯作者：
Link, Wolfgang
影响因子：
4.6
作者：
Kent, D;Bush, EW;Hooper, JE
通讯作者：
Hooper, JE
影响因子：
64.8
作者：
Berger, Michael F.;Lawrence, Michael S.;Demichelis, Francesca;Drier, Yotam;Cibulskis, Kristian;Sivachenko, Andrey Y.;Sboner, Andrea;Esgueva, Raquel;Pflueger, Dorothee;Sougnez, Carrie;Onofrio, Robert;Carter, Scott L.;Park, Kyung;Habegger, Lukas;Ambrogio, Lauren;Fennell, Timothy;Parkin, Melissa;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Pugh, Trevor J.;Wilkinson, Jane;Fisher, Sheila;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Simons, Jonathan W.;Kitabayashi, Naoki;MacDonald, Theresa Y.;Kantoff, Philip W.;Chin, Lynda;Gabriel, Stacey B.;Gerstein, Mark B.;Golub, Todd R.;Meyerson, Matthew;Tewari, Ashutosh;Lander, Eric S.;Getz, Gad;Rubin, Mark A.;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
DOI：
10.1073/pnas.0408918102
发表时间：
2005-05-24
影响因子：
11.1
作者：
Hernádez-Muñoz, I;Lund, AH;van Lohuizen, M
通讯作者：
van Lohuizen, M
影响因子：
64.8
作者：
通讯作者：
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