Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cancer migration

Unjamming tumour cell invasion through cGAS–STING

Nature Materials volume 22, pages 532–533 (2023)Cite this article

Subjects

Locally confined epithelial malignancies undergo a phase transition from a solid-like to liquid-like state, a process called unjamming, where associated chronic intracellular strain causes nuclear envelope rupture, leading to the emergence of pro-metastatic traits due to cGAS–STING pathway activation.

Malignancies that form from normal epithelium are frequently constrained into densely packed, or jammed, masses by the surrounding tissue. This confinement can cause overcrowding and compressive mechanical stresses that can be tumour suppressive and lead to an arrested cellular state. Tumour cells escape from such confinement by cellular unjamming, a recently discovered process that is characterized by a collective motion of cells that is similar to the fluid-like flocking of birds1. This transition is activated by RAB5A, a small G protein that is an important regulator of membrane receptor trafficking and endocytosis2. RAB5A triggers actin remodelling and enhances formation of lamellipodia, cell membrane protrusions that drive the collective motion during unjamming. Now writing in Nature Materials, Frittoli and colleagues demonstrate that the physical stresses involved in the phase transition of cellular unjamming directly rewire the transcriptional state of tumour cells towards a pro-metastatic phenotype3.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Phase transition from solid- to fluid-like invokes a cytosolic DNA response.

References

  1. Giavazzi, F. et al. J. Phys. D 50, 384003 (2017).

    Article  Google Scholar 

  2. Lanzetti, L., Palamidessi, A., Areces, L., Scita, G. & Di Fiore, P. P. Nature 429, 309–314 (2004).

    Article  CAS  Google Scholar 

  3. Frittoli, E. et al. Nat. Mater. https://doi.org/10.1038/s41563-022-01431-x (2022).

    Article  Google Scholar 

  4. Harada, T. et al. J. Cell Biol. 204, 669–682 (2014).

    Article  CAS  Google Scholar 

  5. Bakhoum, S. et al. Nature 553, 467–472 (2018).

    Article  CAS  Google Scholar 

  6. Patel, S. A., Rodrigues, P., Wesolowski, L. & Vanharanta, S. Br. J. Cancer 124, 3–12 (2021).

    Article  CAS  Google Scholar 

  7. Nguyen, B. et al. Cell 185, 563–575.e11 (2022).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

    Matthew Deyell

  2. Human Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Samuel F. Bakhoum

Authors
  1. Matthew Deyell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel F. Bakhoum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Matthew Deyell or Samuel F. Bakhoum.

Ethics declarations

Competing interests

S.F.B. has patents related to targeting chromosomal instability and cGAS–STING signalling in cancer. He also owns equity in, receives compensation from, serves as a consultant to, and is on the Scientific Advisory Board and Board of Directors of, Volastra Therapeutics Inc. M.D. declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deyell, M., Bakhoum, S.F. Unjamming tumour cell invasion through cGAS–STING. Nat. Mater. 22, 532–533 (2023). https://doi.org/10.1038/s41563-023-01542-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41563-023-01542-z

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer