IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30409-1.html
   My bibliography  Save this article

TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling

Author

Listed:
  • Song Gao

    (University of Alabama at Birmingham)

  • Shuaibin Wang

    (University of Alabama at Birmingham)

  • Zhiying Zhao

    (University of Alabama at Birmingham)

  • Chao Zhang

    (University of Alabama at Birmingham)

  • Zhicao Liu

    (University of Alabama at Birmingham)

  • Ping Ye

    (University of Alabama at Birmingham)

  • Zhifang Xu

    (University of Alabama at Birmingham)

  • Baozhu Yi

    (University of Alabama at Birmingham)

  • Kai Jiao

    (University of Alabama at Birmingham)

  • Gurudatta A. Naik

    (University of Alabama at Birmingham)

  • Shi Wei

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Soroush Rais-Bahrami

    (University of Alabama at Birmingham
    University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Sejong Bae

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Wei-Hsiung Yang

    (Mercer University School of Medicine)

  • Guru Sonpavde

    (Dana Farber Cancer Institute)

  • Runhua Liu

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Lizhong Wang

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

Abstract

Human tubulin beta class IVa (TUBB4A) is a member of the β-tubulin family. In most normal tissues, expression of TUBB4A is little to none, but it is highly expressed in human prostate cancer. Here we show that high expression levels of TUBB4A are associated with aggressive prostate cancers and poor patient survival, especially for African-American men. Additionally, in prostate cancer cells, TUBB4A knockout (KO) reduces cell growth and migration but induces DNA damage through increased γH2AX and 53BP1. Furthermore, during constricted cell migration, TUBB4A interacts with MYH9 to protect the nucleus, but either TUBB4A KO or MYH9 knockdown leads to severe DNA damage and reduces the NF-κB signaling response. Also, TUBB4A KO retards tumor growth and metastasis. Functional analysis reveals that TUBB4A/GSK3β binds to the N-terminal of MYH9, and that TUBB4A KO reduces MYH9-mediated GSK3β ubiquitination and degradation, leading to decreased activation of β-catenin signaling and its relevant epithelial-mesenchymal transition. Likewise, prostate-specific deletion of Tubb4a reduces spontaneous tumor growth and metastasis via inhibition of NF-κB, cyclin D1, and c-MYC signaling activation. Our results suggest an oncogenic role of TUBB4A and provide a potentially actionable therapeutic target for prostate cancers with TUBB4A overexpression.

Suggested Citation

  • Song Gao & Shuaibin Wang & Zhiying Zhao & Chao Zhang & Zhicao Liu & Ping Ye & Zhifang Xu & Baozhu Yi & Kai Jiao & Gurudatta A. Naik & Shi Wei & Soroush Rais-Bahrami & Sejong Bae & Wei-Hsiung Yang & Gu, 2022. "TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30409-1
    DOI: 10.1038/s41467-022-30409-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30409-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-30409-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Lizhong Wang & Runhua Liu & Peiying Ye & Chunshu Wong & Guo-Yun Chen & Penghui Zhou & Kaoru Sakabe & Xincheng Zheng & Wei Wu & Peng Zhang & Taijiao Jiang & Michael F. Bassetti & Sandro Jube & Yi Sun &, 2015. "Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    2. Sandra Tavares & André Filipe Vieira & Anna Verena Taubenberger & Margarida Araújo & Nuno Pimpao Martins & Catarina Brás-Pereira & António Polónia & Maik Herbig & Clara Barreto & Oliver Otto & Joana C, 2017. "Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells," Nature Communications, Nature, vol. 8(1), pages 1-18, August.
    3. Daniel A. Fletcher & R. Dyche Mullins, 2010. "Cell mechanics and the cytoskeleton," Nature, Nature, vol. 463(7280), pages 485-492, January.
    4. Cheng-Zhong Zhang & Alexander Spektor & Hauke Cornils & Joshua M. Francis & Emily K. Jackson & Shiwei Liu & Matthew Meyerson & David Pellman, 2015. "Chromothripsis from DNA damage in micronuclei," Nature, Nature, vol. 522(7555), pages 179-184, June.
    5. Hawa-Racine Thiam & Pablo Vargas & Nicolas Carpi & Carolina Lage Crespo & Matthew Raab & Emmanuel Terriac & Megan C. King & Jordan Jacobelli & Arthur S. Alberts & Theresia Stradal & Ana-Maria Lennon-D, 2016. "Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gábor Pete & Ádám Timár & Sigurdur Örn Stefánsson & Ivan Bonamassa & Márton Pósfai, 2024. "Physical networks as network-of-networks," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    2. Chao Jiang & Hong-Yu Luo & Xinpeng Xu & Shuo-Xing Dou & Wei Li & Dongshi Guan & Fangfu Ye & Xiaosong Chen & Ming Guo & Peng-Ye Wang & Hui Li, 2023. "Switch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Heathcliff Dorado García & Fabian Pusch & Yi Bei & Jennifer Stebut & Glorymar Ibáñez & Kristina Guillan & Koshi Imami & Dennis Gürgen & Jana Rolff & Konstantin Helmsauer & Stephanie Meyer-Liesener & N, 2022. "Therapeutic targeting of ATR in alveolar rhabdomyosarcoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Stamatis Papathanasiou & Styliani Markoulaki & Logan J. Blaine & Mitchell L. Leibowitz & Cheng-Zhong Zhang & Rudolf Jaenisch & David Pellman, 2021. "Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    5. Muqing Cao & Xiaoxiao Zou & Chaoyi Li & Zaisheng Lin & Ni Wang & Zhongju Zou & Youqiong Ye & Joachim Seemann & Beth Levine & Zaiming Tang & Qing Zhong, 2023. "An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Peng Shi & Xiaoyu Ren & Jie Meng & Chenlu Kang & Yihe Wu & Yingxue Rong & Shujuan Zhao & Zhaodi Jiang & Ling Liang & Wanzhong He & Yuxin Yin & Xiangdong Li & Yong Liu & Xiaoshuai Huang & Yujie Sun & B, 2022. "Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Frederic Li Mow Chee & Bruno Beernaert & Billie G. C. Griffith & Alexander E. P. Loftus & Yatendra Kumar & Jimi C. Wills & Martin Lee & Jessica Valli & Ann P. Wheeler & J. Douglas Armstrong & Maddy Pa, 2023. "Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Kate M. MacDonald & Shirony Nicholson-Puthenveedu & Maha M. Tageldein & Sarika Khasnis & Cheryl H. Arrowsmith & Shane M. Harding, 2023. "Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Gaurav Luthria & Ran Li & Stephanie Wang & Mark Prytyskach & Rainer H. Kohler & Douglas A. Lauffenburger & Timothy J. Mitchison & Ralph Weissleder & Miles A. Miller, 2020. "In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    10. Yuhang Zhang & Jingyi Du & Xian Liu & Fei Shang & Yunxin Deng & Jiaqing Ye & Yukai Wang & Jie Yan & Hu Chen & Miao Yu & Shimin Le, 2024. "Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Suchet Nanda & Abram Calderon & Arya Sachan & Thanh-Thuy Duong & Johannes Koch & Xiaoyi Xin & Djamschid Solouk-Stahlberg & Yao-Wen Wu & Perihan Nalbant & Leif Dehmelt, 2023. "Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Julian C. Bahr & Xiao-Yan Li & Tamar Y. Feinberg & Long Jiang & Stephen J. Weiss, 2022. "Divergent regulation of basement membrane trafficking by human macrophages and cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    13. Lorenza Garribba & Giuseppina De Feudis & Valentino Martis & Martina Galli & Marie Dumont & Yonatan Eliezer & René Wardenaar & Marica Rosaria Ippolito & Divya Ramalingam Iyer & Andréa E. Tijhuis & Dia, 2023. "Short-term molecular consequences of chromosome mis-segregation for genome stability," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Reena Kumari & Katharina Ven & Megan Chastney & Shrikant B. Kokate & Johan Peränen & Jesse Aaron & Konstantin Kogan & Leonardo Almeida-Souza & Elena Kremneva & Renaud Poincloux & Teng-Leong Chew & Pet, 2024. "Focal adhesions contain three specialized actin nanoscale layers," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    15. Chen Sun & Kunal Kathuria & Sarah B. Emery & ByungJun Kim & Ian E. Burbulis & Joo Heon Shin & Daniel R. Weinberger & John V. Moran & Jeffrey M. Kidd & Ryan E. Mills & Michael J. McConnell, 2024. "Mapping recurrent mosaic copy number variation in human neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    16. Alves Ribeiro, Marcus V. & Jurjiu, Aurel & Galiceanu, Mircea, 2022. "Dynamics of semiflexible generalized scale-free polymer networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 606(C).
    17. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Cannabis- and Substance-Related Epidemiological Patterns of Chromosomal Congenital Anomalies in Europe: Geospatiotemporal and Causal Inferential Study," IJERPH, MDPI, vol. 19(18), pages 1-51, September.
    18. Chrystian Junqueira Alves & Rafael Dariolli & Jonathan Haydak & Sangjo Kang & Theodore Hannah & Robert J. Wiener & Stefanie DeFronzo & Rut Tejero & Gabriele L. Gusella & Aarthi Ramakrishnan & Rodrigo , 2021. "Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion," Nature Communications, Nature, vol. 12(1), pages 1-23, December.
    19. Antoine Vian & Marie Pochitaloff & Shuo-Ting Yen & Sangwoo Kim & Jennifer Pollock & Yucen Liu & Ellen M. Sletten & Otger Campàs, 2023. "In situ quantification of osmotic pressure within living embryonic tissues," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    20. Qin, Xing & Hu, Jianhua & Ma, Shuangge & Wu, Mengyun, 2024. "Estimation of multiple networks with common structures in heterogeneous subgroups," Journal of Multivariate Analysis, Elsevier, vol. 202(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30409-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.