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Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity

Oncogene volume 36, pages 2900–2909 (2017)Cite this article

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A Correction to this article was published on 02 January 2020

Abstract

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that coordinates glycolysis and biosynthesis to promote cancer growth via its metabolic activity. Here, we report the discovery of a non-metabolic function of PGAM1 in promoting cancer metastasis. A proteomic study identified α-smooth muscle actin (ACTA2) as a PGAM1-associated protein. PGAM1 modulated actin filaments assembly, cell motility and cancer cell migration via directly interacting with ACTA2, which was independent of its metabolic activity. The enzymatically inactive H186R mutant retained its association with ACTA2, whereas 201–210 amino acids deleted PGAM1 mutant lost the interaction with ACTA2 regardless of intact metabolic activity. Importantly, PGAM1 knockdown decreased metastatic potential of breast cancer cells in vivo and PGAM1 and ACTA2 were jointly associated with the prognosis of breast cancer patients. Together, this study provided the first evidence revealing a non-metabolic function of PGAM1 in promoting cell migration, and gained new insights into the role of PGAM1 in cancer progression.

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Acknowledgements

This work was supported by the China International Science and Technology Cooperation Program (No. 2015DFM30040 to MH), the National Science and Technology Major Project (No. 2015ZX09101009 to MH), grants from the National Natural Science Foundation of China (No. 81573464 to MH, No. 81321092 to JD) and NSFC-Shandong Joint Fund for Marine Science Research Centers (No. U1406402 to JD)

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Author notes

  1. D Zhang, N Jin and W Sun: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    D Zhang, N Jin, W Sun, X Li, Z Xie, J Qu, J Xu, X Yang, Y Su, S Tang, J Ding, M Huang & M Geng

  2. The Chemical Proteomics Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    B Liu & M Tan

  3. Laboratory of Pharmaceutical Analysis, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

    H Han & D Chen

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Correspondence to M Huang or M Geng.

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Zhang, D., Jin, N., Sun, W. et al. Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity. Oncogene 36, 2900–2909 (2017). https://doi.org/10.1038/onc.2016.446

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