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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550821/
https://www.ncbi.nlm.nih.gov/pubmed/33117682
http://dx.doi.org/10.3389/fonc.2020.544288
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author 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
author_facet 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
author_sort Guo, Wenjing
collection PubMed
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.
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spelling pubmed-75508212020-10-27 Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling 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 Front Oncol Oncology 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. Frontiers Media S.A. 2020-09-29 /pmc/articles/PMC7550821/ /pubmed/33117682 http://dx.doi.org/10.3389/fonc.2020.544288 Text en Copyright © 2020 Guo, Zhang, Li, Lai, Gu, Xu, Chen, Xing, Chen, Qian, Xu, Zeng and Deng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
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
Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling
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 Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550821/
https://www.ncbi.nlm.nih.gov/pubmed/33117682
http://dx.doi.org/10.3389/fonc.2020.544288
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