Menu

Close

Stopping Transformed Growth with Cytoskeletal Proteins: Turning a Devil into an Angel

Bo Yang, Haguy Wolfenson, Naotaka Nakazawa, Shuaimin Liu, Junqiang Hu, Michael Sheetz

Preprint posted on January 27, 2018 https://www.biorxiv.org/content/early/2018/01/27/221176

Michael Sheetz and colleagues provide a deeper understanding of how the differential abundance of cytoskeletal components regulates the mechanism by which mechanical signals are perceived from the extracellular environment

Selected by Jon Humphries

How this work fits the bigger picture

A long-standing test of aberrant control of cell growth that is linked to cancer is the proliferation of cultured cells in soft agar. This assay relies on the observation that cancer cells lose their ability to sense the stiffness of the extracellular matrix, avoid apoptosis, and survive in soft extracellular environments. Cells are intimately linked to extracellular matrix proteins through cell surface receptors, such as integrins, that connect to cytoskeletal structures. Over recent years, the precise mechanisms of how cells relay mechanical signals from the extracellular matrix has been a keen area of active research, and here Michael Sheetz and colleagues build on the role that the cytoskeleton plays in such control.

Key findings

In this provocatively-titled preprint, the authors confirm and extend previous work through a focussed dissection of the relative expression of selected cytoskeletal components. The authors first noted expression differences between normal and cancer cell lines (for morphology, force sensing and cytoskeletal proteins), and then proceeded to show that modulation of various cytoskeletal components (myosin IIa and tropomyosins) was able to control force sensing and growth in soft agar.

What I like about this preprint

I was attracted to this manuscript as it presents data utilising multiple cancer cell lines, which have been transformed by a variety of mechanisms and scales of measurement (time and molecular spatial organisation). Furthermore, the effects were rescue-able through knockdown or over-expression of selected cytoskeletal components. Interestingly, not all cytoskeletal components had equivalent effects, and some (myosin IIb) were unable to rescue the observed phenomena.

Future directions

Taking this work forward, it will be interesting to assess a role for the relative expression of myosin IIa and tropomyosins using in vivo models of cancer. Perhaps this would be achievable in the first instance through the use of tools from the emerging field of cancer organoids? It would also be of interest to see how the observed effects input into other well-described force sensing pathways such as YAP/TAZ cytoplasmic-nuclear shuttling, as these pathways are strongly influenced by the actin cytoskeletal network.

 

Read preprint (1 votes)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cancer biology category:

    Also in the cell biology category:

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Arnaud Monnard

    1

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

    Pierre ROME, Hiroyuki OHKURA



    Selected by Binyam Mogessie

    ERM proteins: The missing actin linkers in clathrin-mediated endocytosis

    Audun Sverre Kvalvaag, Kay Oliver Schink, Andreas Brech, et al.



    Selected by Nicola Stevenson

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

    Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, et al.



    Selected by Penelope La-Borde

    Atomic model of microtubule-bound tau

    Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, et al.



    Selected by Satish Bodakuntla

    1

    Spatial Self-Organization Resolves Conflicts Between Individuality and Collective Migration

    Xiongfei Fu, Setsu Kato, Junjiajia Long, et al.



    Selected by Amanda Haage

    1

    PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery

    Nathalie Conte, Jeremy Mason, Csaba Halmagyi, et al.



    Selected by Carmen Adriaens

    Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

    Girish R. Kale, Xingbo Yang, Jean-Marc Philippe, et al.



    Selected by Arnaud Monnard

    HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells

    Hannah Harrison, Henry J Pegg, Jamie Thompson, et al.



    Selected by Anh Hoang Le

    Higher-Order Organization Principles of Pre-translational mRNPs

    Mihir Metkar, Hakan Ozadam, Bryan R. Lajoie, et al.



    Selected by Carmen Adriaens

    Capturing the onset of PRC2-mediated repressive domain formation

    Ozgur Oksuz, Varun Narendra, Chul-Hwan Lee, et al.



    Selected by Boyan Bonev

    RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs

    Mark A McClintock, Carly I Dix, Christopher M Johnson, et al.

    AND

    Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

    Thomas E. Sladewski, Neil Billington, M. Yusuf Ali, et al.



    Selected by Dmitry Nashchekin
    Close

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.

    Accept