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      Pyruvate Kinase M2 Promotes Prostate Cancer Metastasis Through Regulating ERK1/2-COX-2 Signaling

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          Abstract

          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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          Most cited references49

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          Tumor metastasis: molecular insights and evolving paradigms.

          Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                29 September 2020
                2020
                : 10
                : 544288
                Affiliations
                [1] 1Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, China
                [2] 2Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou, China
                [3] 3Department of Clinical Laboratory, The Fifth Affiliated Hospital, Southern Medical University , Guangzhou, China
                Author notes

                Edited by: Qiongzhu Dong, Fudan University, China

                Reviewed by: Taro Hitosugi, Mayo Clinic, United States; Hsueh-Wei Chang, Kaohsiung Medical University, Taiwan; Sumin Kang, Emory University, United States

                *Correspondence: Fangyin Zeng, zengfy@ 123456126.com

                These authors have contributed equally to this work

                This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2020.544288
                7550821
                33117682
                3bc31e3e-fada-4b44-9588-d329c62d0603
                Copyright © 2020 Guo, Zhang, Li, Lai, Gu, Xu, Chen, Xing, Chen, Qian, Xu, Zeng and Deng.

                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.

                History
                : 20 May 2020
                : 01 September 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 49, Pages: 13, Words: 0
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                pyruvate kinase m2,erk1/2,cyclooxygenase 2,tumor metastasis,prostate cancer

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