Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling
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 can...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.544288/full |
| _version_ | 1828409225955508224 |
|---|---|
| author | Wenjing Guo Wenjing Guo Zhishuai Zhang Guihuan Li Xiaoju Lai Ruonan Gu Ruonan Gu Wanfu Xu Hua Chen Zhe Xing Liping Chen Jiabi Qian Shiyuan Xu Fangyin Zeng Fan Deng |
| author_facet | Wenjing Guo Wenjing Guo Zhishuai Zhang Guihuan Li Xiaoju Lai Ruonan Gu Ruonan Gu Wanfu Xu Hua Chen Zhe Xing Liping Chen Jiabi Qian Shiyuan Xu Fangyin Zeng Fan Deng |
| author_sort | Wenjing Guo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:52:36Z |
| format | Article |
| id | doaj.art-9c9737860b76451fbe1d04cb7f90c958 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T11:52:36Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-9c9737860b76451fbe1d04cb7f90c9582022-12-22T01:49:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-09-011010.3389/fonc.2020.544288544288Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 SignalingWenjing Guo0Wenjing Guo1Zhishuai Zhang2Guihuan Li3Xiaoju Lai4Ruonan Gu5Ruonan Gu6Wanfu Xu7Hua Chen8Zhe Xing9Liping Chen10Jiabi Qian11Shiyuan Xu12Fangyin Zeng13Fan Deng14Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Clinical Laboratory, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaPyruvate 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.https://www.frontiersin.org/article/10.3389/fonc.2020.544288/fullpyruvate kinase M2ERK1/2cyclooxygenase 2tumor metastasisprostate cancer |
| spellingShingle | Wenjing Guo Wenjing Guo Zhishuai Zhang Guihuan Li Xiaoju Lai Ruonan Gu Ruonan Gu Wanfu Xu Hua Chen Zhe Xing Liping Chen Jiabi Qian Shiyuan Xu Fangyin Zeng Fan Deng Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling Frontiers in Oncology pyruvate kinase M2 ERK1/2 cyclooxygenase 2 tumor metastasis prostate cancer |
| title | Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling |
| title_full | Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling |
| title_fullStr | Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling |
| title_full_unstemmed | Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling |
| title_short | Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling |
| title_sort | pyruvate kinase m2 promotes prostate cancer metastasis through regulating erk1 2 cox 2 signaling |
| topic | pyruvate kinase M2 ERK1/2 cyclooxygenase 2 tumor metastasis prostate cancer |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.544288/full |
| work_keys_str_mv | AT wenjingguo pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT wenjingguo pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT zhishuaizhang pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT guihuanli pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT xiaojulai pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT ruonangu pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT ruonangu pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT wanfuxu pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT huachen pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT zhexing pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT lipingchen pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT jiabiqian pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT shiyuanxu pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT fangyinzeng pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling AT fandeng pyruvatekinasem2promotesprostatecancermetastasisthroughregulatingerk12cox2signaling |