Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling.
Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling.
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丙酮酸激酶 M2 通过调节 ERK1/2-COX-2 信号传导促进前列腺癌转移
DOI：
10.3389/fonc.2020.544288
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发表时间：
2020
影响因子：
4.7
通讯作者：
Deng F
中科院分区：
文献类型：
--
作者：
Guo W;Zhang Z;Li G;Lai X;Gu R;Xu W;Chen H;Xing Z;Chen L;Qian J;Xu S;Zeng F;Deng F
丙酮酸激酶M2(PKM2)是糖酵解的关键酶，在多种肿瘤细胞中高表达，在肿瘤的进展和转移中起重要作用。然而，PKM2在肿瘤转移中的作用仍不清楚。我们发现PKM2通过细胞外调节蛋白激酶(ERK)-环氧合酶(COX-2)信号通路促进前列腺癌的转移。基于公共数据库，我们发现PKM2在前列腺癌中表达上调，并与肿瘤转移呈正相关。进一步分析表明，PKM2通过上调COX-2的表达促进前列腺癌细胞的迁移/侵袭和上皮-间充质转化(EMT)。通过IP和芯片检测，从机制上讲，PKM2与ERK1/2相互作用并调节其磷酸化，导致ERK1/2下游转录因子c-jun的磷酸化，从而激活COX-2的转录，而抑制COX-2则显著逆转了PKM2促进体内肿瘤转移的作用。综上所述，我们的结果提示，一个新的PKM2-ERK1/2-c-Jun-COX-2轴是控制前列腺癌转移的潜在靶点。
Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis, which is highly expressed in many tumor cells, and has emerged as an important player in tumor progression and metastasis. However, the functional roles of PKM2 in tumor metastasis remain elusive. Here we showed that PKM2 promoted prostate cancer metastasis via extracellular-regulated protein kinase (ERK)–cyclooxygenase (COX-2) signaling. Based on public databases, we found that PKM2 expression was upregulated in prostate cancer and positively associated with tumor metastasis. Further analysis showed that PKM2 promoted prostate cancer cell migration/invasion and epithelial–mesenchymal transition (EMT) through upregulation of COX-2. Mechanistically, PKM2 interacted with ERK1/2 and regulated its phosphorylation, leading to phosphorylation of transcription factor c-Jun, downstream of ERK1/2, to activate COX-2 transcription by IP and ChIP assay, while inhibition of COX-2 significantly reversed the promotion effect of PKM2 on tumor metastasis in vivo. Taken together, our results suggest that a novel of PKM2–ERK1/2–c-Jun–COX-2 axis is a potential target in controlling prostate cancer metastasis.
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影响因子：
4
作者：
Ma, Rong;Liu, Qing;Lu, Xiaomei
通讯作者：
Lu, Xiaomei
影响因子：
6.4
作者：
Liu, Vivian M.;Vander Heiden, Matthew G.
通讯作者：
Vander Heiden, Matthew G.
影响因子：
37.3
作者：
Hsu MC;Hung WC
通讯作者：
Hung WC
影响因子：
3.7
作者：
Buetti-Dinh A;O'Hare T;Friedman R
通讯作者：
Friedman R
DOI：
10.12659/msm.901542
发表时间：
2017-04-27
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Cheng KY;Hao M
通讯作者：
Hao M