IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39281-z.html
   My bibliography  Save this article

CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling

Author

Listed:
  • Guillaume Serwe

    (Université de Montréal
    Université de Montréal)

  • David Kachaner

    (Université de Montréal)

  • Jessica Gagnon

    (Université de Montréal
    Université de Montréal)

  • Cédric Plutoni

    (Université de Montréal)

  • Driss Lajoie

    (Université de Montréal)

  • Eloïse Duramé

    (Université de Montréal
    Université de Montréal)

  • Malha Sahmi

    (Université de Montréal)

  • Damien Garrido

    (Université de Montréal)

  • Martin Lefrançois

    (Université de Montréal)

  • Geneviève Arseneault

    (Université de Montréal)

  • Marc K. Saba-El-Leil

    (Université de Montréal)

  • Sylvain Meloche

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Gregory Emery

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

  • Marc Therrien

    (Université de Montréal
    Université de Montréal
    Université de Montréal)

Abstract

Cell motility is a critical feature of invasive tumour cells that is governed by complex signal transduction events. Particularly, the underlying mechanisms that bridge extracellular stimuli to the molecular machinery driving motility remain partially understood. Here, we show that the scaffold protein CNK2 promotes cancer cell migration by coupling the pro-metastatic receptor tyrosine kinase AXL to downstream activation of ARF6 GTPase. Mechanistically, AXL signalling induces PI3K-dependent recruitment of CNK2 to the plasma membrane. In turn, CNK2 stimulates ARF6 by associating with cytohesin ARF GEFs and with a novel adaptor protein called SAMD12. ARF6-GTP then controls motile forces by coordinating the respective activation and inhibition of RAC1 and RHOA GTPases. Significantly, genetic ablation of CNK2 or SAMD12 reduces metastasis in a mouse xenograft model. Together, this work identifies CNK2 and its partner SAMD12 as key components of a novel pro-motility pathway in cancer cells, which could be targeted in metastasis.

Suggested Citation

  • Guillaume Serwe & David Kachaner & Jessica Gagnon & Cédric Plutoni & Driss Lajoie & Eloïse Duramé & Malha Sahmi & Damien Garrido & Martin Lefrançois & Geneviève Arseneault & Marc K. Saba-El-Leil & Syl, 2023. "CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39281-z
    DOI: 10.1038/s41467-023-39281-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39281-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39281-z?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. Tsunaki Hongu & Yuji Funakoshi & Shigetomo Fukuhara & Teruhiko Suzuki & Susumu Sakimoto & Nobuyuki Takakura & Masatsugu Ema & Satoru Takahashi & Susumu Itoh & Mitsuyasu Kato & Hiroshi Hasegawa & Naoki, 2015. "Arf6 regulates tumour angiogenesis and growth through HGF-induced endothelial β1 integrin recycling," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    2. Afnan Abu-Thuraia & Marie-Anne Goyette & Jonathan Boulais & Carine Delliaux & Chloé Apcher & Céline Schott & Rony Chidiac & Halil Bagci & Marie-Pier Thibault & Dominique Davidson & Mathieu Ferron & An, 2020. "AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    3. Sandrine Etienne-Manneville & Alan Hall, 2002. "Rho GTPases in cell biology," Nature, Nature, vol. 420(6916), pages 629-635, December.
    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. Jocelyn E. Chau & Kimberly J. Vish & Titus J. Boggon & Amy L. Stiegler, 2022. "SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Limei Wu & Srinivas Chatla & Qiqi Lin & Fabliha Ahmed Chowdhury & Werner Geldenhuys & Wei Du, 2021. "Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Gabriela Casanova-Sepúlveda & Joel A. Sexton & Benjamin E. Turk & Titus J. Boggon, 2023. "Autoregulation of the LIM kinases by their PDZ domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Cummings, F.W, 2004. "A model of morphogenesis," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 339(3), pages 531-547.
    5. Steffen Nørgaard & Shuer Deng & Wei Cao & Roger Pocock, 2018. "Distinct CED-10/Rac1 domains confer context-specific functions in development," PLOS Genetics, Public Library of Science, vol. 14(9), pages 1-24, September.
    6. Josefine Radke & Elisa Schumann & Julia Onken & Randi Koll & Güliz Acker & Bohdan Bodnar & Carolin Senger & Sascha Tierling & Markus Möbs & Peter Vajkoczy & Anna Vidal & Sandra Högler & Petra Kodajova, 2022. "Decoding molecular programs in melanoma brain metastases," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    7. Rashmi Priya & Guillermo A Gomez & Srikanth Budnar & Bipul R Acharya & Andras Czirok & Alpha S Yap & Zoltan Neufeld, 2017. "Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions," PLOS Computational Biology, Public Library of Science, vol. 13(3), pages 1-19, March.
    8. Yasuo Takashima & Atsushi Kawaguchi & Junya Fukai & Yasuo Iwadate & Koji Kajiwara & Hiroaki Hondoh & Ryuya Yamanaka, 2021. "Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma," PLOS ONE, Public Library of Science, vol. 16(6), pages 1-14, June.
    9. Serena Petracchini & Daniel Hamaoui & Anne Doye & Atef Asnacios & Florian Fage & Elisa Vitiello & Martial Balland & Sebastien Janel & Frank Lafont & Mukund Gupta & Benoit Ladoux & Jerôme Gilleron & Te, 2022. "Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    10. Juan Manuel Ortiz-Sanchez & Sara E Nichols & Jacqueline Sayyah & Joan Heller Brown & J Andrew McCammon & Barry J Grant, 2012. "Identification of Potential Small Molecule Binding Pockets on Rho Family GTPases," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-13, July.
    11. Michael J. Roy & Minglyanna G. Surudoi & Ashleigh Kropp & Jianmei Hou & Weiwen Dai & Joshua M. Hardy & Lung-Yu Liang & Thomas R. Cotton & Bernhard C. Lechtenberg & Toby A. Dite & Xiuquan Ma & Roger J., 2023. "Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Luís António Menezes Carreira & Dobromir Szadkowski & Stefano Lometto & Georg. K. A. Hochberg & Lotte Søgaard-Andersen, 2023. "Molecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:14:y:2023:i:1:d:10.1038_s41467-023-39281-z. 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.