Guo Wenjing, Zhang Zhishuai, Li Guihuan, Lai Xiaoju, Gu Ruonan, Xu Wanfu, Chen Hua, Xing Zhe, Chen Liping, Qian Jiabi, Xu Shiyuan, Zeng Fangyin, Deng Fan
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Front Oncol. 2020 Sep 29;10:544288. doi: 10.3389/fonc.2020.544288. eCollection 2020.
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 . 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.
丙酮酸激酶M2（PKM2）是糖酵解的关键酶，在许多肿瘤细胞中高表达，并已成为肿瘤进展和转移中的重要角色。然而，PKM2在肿瘤转移中的功能作用仍不清楚。在此我们表明，PKM2通过细胞外调节蛋白激酶（ERK）-环氧化酶（COX-2）信号通路促进前列腺癌转移。基于公共数据库，我们发现PKM2在前列腺癌中表达上调，且与肿瘤转移呈正相关。进一步分析表明，PKM2通过上调COX-2促进前列腺癌细胞迁移/侵袭和上皮-间质转化（EMT）。机制上，PKM2与ERK1/2相互作用并调节其磷酸化，导致ERK1/2下游的转录因子c-Jun磷酸化，通过IP和ChIP实验激活COX-2转录，而抑制COX-2可显著逆转PKM2对肿瘤转移的促进作用。综上所述，我们的结果表明，PKM2-ERK1/2-c-Jun-COX-2轴这一新型通路是控制前列腺癌转移的潜在靶点。
