1. Cancer Biology
  2. Cell Biology
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Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling

  1. Yingqi Liu
  2. Lingling Li
  3. Xiaoqing Liu
  4. Yibo Wang
  5. Lingxia Liu
  6. Lu Peng
  7. Jiayuan Liu
  8. Lian zhang
  9. Guannan Wang
  10. Hongyuan Li
  11. Dongxu Liu
  12. Baiqu Huang
  13. Jun Lu  Is a corresponding author
  14. Yu Zhang  Is a corresponding author
  1. Northeast Normal University, China
  2. Chinese Academy of Sciences, China
  3. Auckland University of Technology, New Zealand
Research Article
  • Cited 4
  • Views 2,577
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Cite this article as: eLife 2020;9:e57617 doi: 10.7554/eLife.57617

Abstract

Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal FAK/cortactin signals in vitro and in vivo. Consistently, all the levels of PRMT7, methylated SHANK2, FAK Y397 phosphorylation and cortactin Y421 phosphorylation were correlated with aggressive clinical breast cancer tissues. These findings characterize the PRMT7-dependent SHANK2 methylation as a key player in mediating endosomal FAK signals activation, also point to the value of SHANK2 R240 methylation as a target for breast cancer metastasis.

Data availability

PDB accession number for SHANK2 structure analyse is pdb5G4X. Analysis of SHANK2 gene expression in human tissues using the Human Protein Atlas data.

The following previously published data sets were used

Article and author information

Author details

  1. Yingqi Liu

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3934-0673
  2. Lingling Li

    The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaoqing Liu

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yibo Wang

    Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lingxia Liu

    The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Lu Peng

    The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Jiayuan Liu

    The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Lian zhang

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Guannan Wang

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Hongyuan Li

    Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Dongxu Liu

    School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  12. Baiqu Huang

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Jun Lu

    The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
    For correspondence
    luj809@nenu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  14. Yu Zhang

    The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China
    For correspondence
    zhangy288@nenu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3702-6541

Funding

National Natural Science Foundation of China (31870765)

  • Baiqu Huang

National Natural Science Foundation of China (31571317)

  • Jun Lu

National Natural Science Foundation of China (31570718)

  • Baiqu Huang

National Natural Science Foundation of China (31771335)

  • Yu Zhang

National Natural Science Foundation of China (31770825)

  • Jun Lu

National Natural Science Foundation of China (21807098)

  • Yibo Wang

Natural Science Foundation of Jilin Province (20180101232JC)

  • Jun Lu

Natural Science Foundation of Jilin Province (20180101234JC)

  • Yu Zhang

Natural Science Foundation of Jilin Province (20200404106YY)

  • Yu Zhang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal works were conducted in accordance with the IACUC guidelines and with the protocol approved by the IACUC at the Northeast Normal University, reference assurance number AP2013011.

Human subjects: Human breast tumour specimens were obtained from the Second Hospital of Jilin University, China. All the breast cancer tissue samples were collected from 27 patients enrolled on pathology department of the Second Hospital of Jilin University. All the samples were diagnosed by the pathology department of the Second Hospital of Jilin University to determine the stage and subtype of the breast tumour. This experiment is an immunohistochemical study, no informed consent was needed due to the use of post-diagnostic left-over material. Ethical approval was obtained from the Ethics Review Committee of the Second Hospital of Jilin University (2019-107).

Reviewing Editor

  1. Lynne-Marie Postovit, University of Alberta, Canada

Publication history

  1. Received: April 6, 2020
  2. Accepted: August 25, 2020
  3. Accepted Manuscript published: August 26, 2020 (version 1)
  4. Version of Record published: September 16, 2020 (version 2)

Copyright

© 2020, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    2. Cell Biology
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