Can I read Non-cell-autonomous Cancer Progression from Chromosomal Instability on EtoBox?

Non-cell-autonomous Cancer Progression from Chromosomal Instability by Jun Li; Melissa J. Hubisz; Ethan M. Earlie; Mercedes A. Duran; Christy Hong; Austin A. Varela; Emanuele Lettera; Matthew Deyell; Bernardo Tavora; Jonathan J. Havel; Su M. Phyu; Amit Dipak Amin; Karolina Budre; Erina Kamiya; Julie-Ann Cavallo; Christopher Garris; Simon Powell; Jorge S. Reis-Filho; Hannah Wen; Sarah Bettigole; Atif J. Khan; Benjamin Izar; Eileen E. Parkes; Ashley M. Laughney; Samuel F. Bakhoum is a Physics and Astronomy article available to read on EtoBox.

What is Non-cell-autonomous Cancer Progression from Chromosomal Instability about?

Chromosomal instability (CIN) is a driver of cancer metastasis^1–4^, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing—a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell–cell interactions from single-cell transcriptomic data—we show that CIN-induced chronic activation of the cGAS–STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated wi

Who reads Non-cell-autonomous Cancer Progression from Chromosomal Instability?

Author

Jun Li; Melissa J. Hubisz; Ethan M. Earlie; Mercedes A. Duran; Christy Hong; Austin A. Varela; Emanuele Lettera; Matthew Deyell; Bernardo Tavora; Jonathan J. Havel; Su M. Phyu; Amit Dipak Amin; Karolina Budre; Erina Kamiya; Julie-Ann Cavallo; Christopher Garris; Simon Powell; Jorge S. Reis-Filho; Hannah Wen; Sarah Bettigole; Atif J. Khan; Benjamin Izar; Eileen E. Parkes; Ashley M. Laughney; Samuel F. Bakhoum

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Physics and Astronomy (Physical Sciences)