IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v485y2012i7396d10.1038_nature10912.html
   My bibliography  Save this article

The translational landscape of mTOR signalling steers cancer initiation and metastasis

Author

Listed:
  • Andrew C. Hsieh

    (Helen Diller Family Comprehensive Cancer Center, University of California
    University of California)

  • Yi Liu

    (Intellikine Inc.)

  • Merritt P. Edlind

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Nicholas T. Ingolia

    (Carnegie Institution for Science)

  • Matthew R. Janes

    (Intellikine Inc.)

  • Annie Sher

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Evan Y. Shi

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Craig R. Stumpf

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Carly Christensen

    (Helen Diller Family Comprehensive Cancer Center, University of California)

  • Michael J. Bonham

    (University of California)

  • Shunyou Wang

    (Intellikine Inc.)

  • Pingda Ren

    (Intellikine Inc.)

  • Michael Martin

    (Intellikine Inc.)

  • Katti Jessen

    (Intellikine Inc.)

  • Morris E. Feldman

    (Howard Hughes Medical Institute, University of California)

  • Jonathan S. Weissman

    (Howard Hughes Medical Institute, University of California)

  • Kevan M. Shokat

    (Howard Hughes Medical Institute, University of California)

  • Christian Rommel

    (Intellikine Inc.)

  • Davide Ruggero

    (Helen Diller Family Comprehensive Cancer Center, University of California)

Abstract

The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the ‘cancerous’ translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted.

Suggested Citation

  • Andrew C. Hsieh & Yi Liu & Merritt P. Edlind & Nicholas T. Ingolia & Matthew R. Janes & Annie Sher & Evan Y. Shi & Craig R. Stumpf & Carly Christensen & Michael J. Bonham & Shunyou Wang & Pingda Ren &, 2012. "The translational landscape of mTOR signalling steers cancer initiation and metastasis," Nature, Nature, vol. 485(7396), pages 55-61, May.
    • Handle: RePEc:nat:nature:v:485:y:2012:i:7396:d:10.1038_nature10912
    DOI: 10.1038/nature10912
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10912
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10912?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guo-dong Cao & Xing-yu Xu & Jia-wei Zhang & Bo Chen & Mao-ming Xiong, 2016. "Phosphorylated Mammalian Target of Rapamycin p-mTOR Is a Favorable Prognostic Factor than mTOR in Gastric Cancer," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-16, December.
    2. Kathrin Leppek & Gun Woo Byeon & Wipapat Kladwang & Hannah K. Wayment-Steele & Craig H. Kerr & Adele F. Xu & Do Soon Kim & Ved V. Topkar & Christian Choe & Daphna Rothschild & Gerald C. Tiu & Roger We, 2022. "Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. Fajin Li & Jianhuo Fang & Yifan Yu & Sijia Hao & Qin Zou & Qinglin Zeng & Xuerui Yang, 2023. "Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Stéphanie Kaeser-Pebernard & Christine Vionnet & Muriel Mari & Devanarayanan Siva Sankar & Zehan Hu & Carole Roubaty & Esther Martínez-Martínez & Huiyuan Zhao & Miguel Spuch-Calvar & Alke Petri-Fink &, 2022. "mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1," Nature Communications, Nature, vol. 13(1), pages 1-21, 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:nature:v:485:y:2012:i:7396:d:10.1038_nature10912. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.