IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v578y2020i7796d10.1038_s41586-020-1998-1.html
   My bibliography  Save this article

Mechanical regulation of glycolysis via cytoskeleton architecture

Author

Listed:
  • Jin Suk Park

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Christoph J. Burckhardt

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Rossana Lazcano

    (UT MD Anderson Cancer Center)

  • Luisa M. Solis

    (UT MD Anderson Cancer Center)

  • Tadamoto Isogai

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Linqing Li

    (Harvard University
    Boston University)

  • Christopher S. Chen

    (Harvard University
    Boston University)

  • Boning Gao

    (UT Southwestern Medical Center)

  • John D. Minna

    (UT Southwestern Medical Center)

  • Robert Bachoo

    (UT Southwestern Medical Center)

  • Ralph J. DeBerardinis

    (UT Southwestern Medical Center
    UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Gaudenz Danuser

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

Abstract

The mechanics of the cellular microenvironment continuously modulates cell functions such as growth, survival, apoptosis, differentiation and morphogenesis via cytoskeletal remodelling and actomyosin contractility1–3. Although all of these processes consume energy4,5, it is unknown whether and how cells adapt their metabolic activity to variable mechanical cues. Here we report that the transfer of human bronchial epithelial cells from stiff to soft substrates causes a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme phosphofructokinase (PFK). PFK degradation is triggered by the disassembly of stress fibres, which releases the PFK-targeting E3 ubiquitin ligase tripartite motif (TRIM)-containing protein 21 (TRIM21). Transformed non-small-cell lung cancer cells, which maintain high glycolytic rates regardless of changing environmental mechanics, retain PFK expression by downregulating TRIM21, and by sequestering residual TRIM21 on a stress-fibre subset that is insensitive to substrate stiffness. Our data reveal a mechanism by which glycolysis responds to architectural features of the actomyosin cytoskeleton, thus coupling cell metabolism to the mechanical properties of the surrounding tissue. These processes enable normal cells to tune energy production in variable microenvironments, whereas the resistance of the cytoskeleton in response to mechanical cues enables the persistence of high glycolytic rates in cancer cells despite constant alterations of the tumour tissue.

Suggested Citation

  • Jin Suk Park & Christoph J. Burckhardt & Rossana Lazcano & Luisa M. Solis & Tadamoto Isogai & Linqing Li & Christopher S. Chen & Boning Gao & John D. Minna & Robert Bachoo & Ralph J. DeBerardinis & Ga, 2020. "Mechanical regulation of glycolysis via cytoskeleton architecture," Nature, Nature, vol. 578(7796), pages 621-626, February.
  • Handle: RePEc:nat:nature:v:578:y:2020:i:7796:d:10.1038_s41586-020-1998-1
    DOI: 10.1038/s41586-020-1998-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-1998-1
    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/s41586-020-1998-1?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
    ---><---

    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. Jorge Barbazan & Carlos Pérez-González & Manuel Gómez-González & Mathieu Dedenon & Sophie Richon & Ernest Latorre & Marco Serra & Pascale Mariani & Stéphanie Descroix & Pierre Sens & Xavier Trepat & D, 2023. "Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Sara G. Romeo & Ilaria Secco & Edoardo Schneider & Christina M. Reumiller & Celio X. C. Santos & Anna Zoccarato & Vishal Musale & Aman Pooni & Xiaoke Yin & Konstantinos Theofilatos & Silvia Cellone Tr, 2023. "Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Yi Zhang & Mingjie Wang & Ling Ye & Shengqi Shen & Yuxi Zhang & Xiaoyu Qian & Tong Zhang & Mengqiu Yuan & Zijian Ye & Jin Cai & Xiang Meng & Shiqiao Qiu & Shengzhi Liu & Rui Liu & Weidong Jia & Xianzh, 2024. "HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Akifumi Shiomi & Taikopaul Kaneko & Kaori Nishikawa & Arata Tsuchida & Takashi Isoshima & Mayuko Sato & Kiminori Toyooka & Kentaro Doi & Hidekazu Nishikii & Hirofumi Shintaku, 2024. "High-throughput mechanical phenotyping and transcriptomics of single cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Du Wenqiang & Ashkan Novin & Yamin Liu & Junaid Afzal & Yasir Suhail & Shaofei Liu & Nicole R. Gavin & Jennifer R. Jorgensen & Christopher M. Morosky & Reinaldo Figueroa & Tannin A. Schmidt & Melinda , 2024. "Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Ashenafi Bulle & Peng Liu & Kuljeet Seehra & Sapana Bansod & Yali Chen & Kiran Zahra & Vikas Somani & Iftikhar Ali Khawar & Hung-Po Chen & Paarth B. Dodhiawala & Lin Li & Yutong Geng & Chia-Kuei Mo & , 2024. "Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:578:y:2020:i:7796:d:10.1038_s41586-020-1998-1. 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.

    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.