PPM1A is a RelA phosphatase with tumor suppressor-like activity.
PPM1A is a RelA phosphatase with tumor suppressor-like activity.
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作者：
核因子-κB（NF-κB）信号促进了人类疾病，尤其是炎症性疾病，NF-κB在肿瘤和肿瘤的生长中具有作用，并促进了导致NF-κB激活的机制磷酸化的磷酸化促进促进致癌行为表明，靶向肿瘤的磷酸酶可以鉴定出肿瘤磷酸酶的活性。 F-κB转录活性，导致单核细胞趋化蛋白1/趋化因子（C型基序）的表达降低，植入癌症转移的细胞因子植入了PPM1A的细胞因子。蚂蚁转移。揭示了PPM1A的表达抑制了血管注射后前列腺癌细胞的奖励转移，我们的发现表明，PPM1A是一种调节NF-κB活性的RERA磷酸酶，并且PPM1A对PPM1A的分析也没有ppm1a的分析。描述了PPM1A活性的增加在肿瘤中，代表了抑制人类癌症中NF-κB信号传导或奖励转移的潜在治疗策略。
Nuclear factor-κB (NF-κB) signaling contributes to human disease processes, notably inflammatory diseases and cancer. NF-κB has a role in tumorigenesis and tumor growth, as well as promotion of metastases. Mechanisms responsible for abnormal NF-κB activation are not fully elucidated; however, RelA phosphorylation, particularly at serine residues S536 and S276, is critical for RelA function. Kinases that phosphorylate RelA promote oncogenic behaviors, suggesting that phosphatases targeting RelA could have tumor-inhibiting activities; however, few RelA phosphatases have been identified. Here, we identified tumor inhibitory and RelA phosphatase activities of the protein phosphatase 2C (PP2C) phosphatase family member, PPM1A. We show that PPM1A directly dephosphorylated RelA at residues S536 and S276 and selectively inhibited NF-κB transcriptional activity, resulting in decreased expression of monocyte chemotactic protein-1/chemokine (C–C motif) ligand 2 and interleukin-6, cytokines implicated in cancer metastasis. PPM1A depletion enhanced NF-κB-dependent cell invasion, whereas PPM1A expression inhibited invasion. Analyses of human expression data revealed that metastatic prostate cancer deposits had lower PPM1A expression compared with primary tumors without distant metastases. A hematogenous metastasis mouse model revealed that PPM1A expression inhibited bony metastases of prostate cancer cells after vascular injection. In summary, our findings suggest that PPM1A is a RelA phosphatase that regulates NF-κB activity and that PPM1A has tumor suppressor-like activity. Our analyses also suggest that PPM1A inhibits prostate cancer metastases and as neither gene deletions nor inactivating mutations of PPM1A have been described, increasing PPM1A activity in tumors represents a potential therapeutic strategy to inhibit NF-κB signaling or bony metastases in human cancer.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
4
作者：
Drake, Justin M.;Gabriel, Curtis L.;Henry, Michael D.
通讯作者：
Henry, Michael D.
PP2Calpha在细胞生长，放射性和化学敏感性以及致瘤性中的作用。
影响因子：
37.3
作者：
Lammers, Twan;Peschke, Peter;Ehemann, Volker;Debus, Jurgen;Slobodin, Boris;Lavi, Sara;Huber, Peter
通讯作者：
Huber, Peter
DOI：
10.1158/1078-0432.ccr-09-1352
发表时间：
2009-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arun P;Brown MS;Ehsanian R;Chen Z;Van Waes C
通讯作者：
Van Waes C
影响因子：
4.8
作者：
Buss, H;Dörrie, A;Kracht, M
通讯作者：
Kracht, M