Menu

Close

Mechanical Stretch Kills Transformed Cancer Cells

Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, Yasaman Nematbakhsh, Anushya Hariharan, Chwee Teck Lim, Michael Sheetz

Preprint posted on December 10, 2018 https://www.biorxiv.org/content/10.1101/491746v2

Forcefully aiming at cancer cells

Selected by Vibha SINGH

Categories: cell biology

Context

A hallmark of transformed cancer cells is their ability to grow on soft substrate, which is often correlated with their loss of matrix rigidity-sensing ability 1. Previous studies demonstrated that alteration in expression of cytoskeleton proteins in transformed cancer cells could restore rigidity sensing and help in blocking growth 2,3. Recent studies have provided some evidence in support of mechanical force-dependent growth inhibition in a mice model; gentle stretching of mice (10 minutes of stretching/day for 4-weeks) resulted in inhibition of tumor growth 4,5. Authors of this preprint report a very intriguing finding that transformed cancer cells from various tissue origins, when subjected to cyclic mechanical stretching, inhibit their growth and undergo apoptosis.

 

Key findings

The authors show that 6 hours of cyclic stretching of rigidity-dependent transformed cancer cells, which lack expression of cytoskeletal protein TPM2.1 (key protein in rigidity sensing 6), results in cell elongation. Exogenous expression of TPM2.1 could restore rigidity sensing, and inhibited cyclic-stretching-dependent cell elongation. Further, the authors report that cyclic stretching inhibited the growth of transformed cells, while facilitating normal cell growth. This was attributed to increased apoptosis in transformed cells and reduced apoptosis in normal cells upon cyclic stretching.

The authors perform elegant experiments to elucidate a mechanistic pathway of this process: cyclic stretching results in increases in the influx of calcium, which activates calpain protease. This further acts on Bax to induce the mitochondrial apoptotic pathway, eventually leading to cell death.

Importance and Future questions

This study reveals that mechanical sensitivity of tumor cells is related to transformed cell state and not linked to tissue origin or cell type. This raises the possibility to exploit this process in animal models to specifically damage tumor cells and simultaneously promote normal cell growth.  These findings will help in understanding and designing a better set up to utilize mechanical force based therapy.

It would be interesting to see when the growth of “normal cells” post cyclic stretching comes down to the non-stretched state. Do the normal cells in a mixture of transformed cancer cells have a mechanoprotective role?

 

References.

  1. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).
  2. Yang, B. et al. Stopping Transformed Growth with Cytoskeletal Proteins: Turning a Devil into an Angel. bioRxiv 221176 (2018). doi:10.1101/221176
  3. Wolfenson, H. et al. Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices. Nat. Cell Biol. 18, 33–42 (2016).
  4. Berrueta, L. et al. Stretching Reduces Tumor Growth in a Mouse Breast Cancer Model. Sci. Rep. 8, 7864 (2018).
  5. Betof, A. S. et al. Modulation of Murine Breast Tumor Vascularity, Hypoxia, and Chemotherapeutic Response by Exercise. JNCI J. Natl. Cancer Inst. 107, (2015).
  6. Stehn, J. R. et al. A Novel Class of Anticancer Compounds Targets the Actin Cytoskeleton in Tumor Cells. Cancer Res. 73, 5169–5182 (2013).

 

Tags: cell stretching, mechanical force, transformed cancer cells

Posted on: 5th February 2019

Read preprint (No Ratings Yet)




  • Have your say

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

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

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

    Register here

    Also in the cell biology category:

    A DNA-based voltmeter for organelles

    Anand Saminathan, John Devany, Kavya S Pillai, et al.



    Selected by Robert Mahen

    Central spindle microtubules are strongly coupled to chromosomes during both anaphase A and anaphase B

    Che-Hang Yu, Stefanie Redemann, Hai-Yin Wu, et al.



    Selected by Federico Pelisch

    1

    Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division

    Evgeny Zatulovskiy, Daniel F. Berenson, Benjamin R. Topacio, et al.



    Selected by Zaki Ahmad

    1

    Minimal membrane interactions conferred by Rheb C-terminal farnesylation are essential for mTORC1 activation

    Shawn M Ferguson, Brittany Angarola



    Selected by Sandra Malmgren Hill

    EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake

    Claudia Matthaeus, Ines Lahmann, Severine Kunz, et al.



    Selected by Andreas Müller

    1

    Mechanical Stretch Kills Transformed Cancer Cells

    Ajay Tijore, Mingxi Yao, Yu-Hsiu Wang, et al.



    Selected by Joseph Jose Thottacherry

    Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells

    Jayashree Chadchankar, Victoria Korboukh, Peter Doig, et al.



    Selected by Mila Basic

    A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart

    Hessel Honkoop, Dennis de Bakker, Alla Aharonov, et al.



    Selected by Andreas van Impel

    1

    S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion.

    Keith T Woodley, Mark O Collins



    Selected by Abagael Lasseigne

    3

    A complex containing lysine-acetylated actin inhibits the formin INF2

    Mu A, Tak Shun Fung, Arminja N. Kettenbach, et al.



    Selected by Laura McCormick

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    1

    Actomyosin-II facilitates long-range retrograde transport of large cargoes by controlling axonal radial contractility

    Tong Wang, Wei Li, Sally Martin, et al.



    Selected by Ivana Viktorinová

    Atlas of Subcellular RNA Localization Revealed by APEX-seq

    Furqan M Fazal, Shuo Han, Pornchai Kaewsapsak, et al.

    AND

    Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules

    Alejandro Padron, Shintaro Iwasaki, Nicholas Ingolia



    Selected by Christian Bates

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    Stable knockout and complementation of receptor expression using in vitro cell line derived reticulocytes for dissection of host malaria invasion requirements

    Timothy J Satchwell, Katherine E Wright, Katy L Haydn-Smith, et al.



    Selected by Alyson Smith
    Close