Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response

Chen Lior, Debra Barki, Coral Halperin, Christine A. Iacobuzio-Donahue, David Kelsen, Ruth Scherz Shouval*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
28 Downloads (Pure)

Abstract

The tumor microenvironment (TME) presents cells with challenges such as variable pH, hypoxia, and free radicals, triggering stress responses that affect cancer progression. In this study, we examine the stress response landscape in four carcinomas—breast, pancreas, ovary, and prostate—across five pathways: heat shock, oxidative stress, hypoxia, DNA damage, and unfolded protein stress. Using a combination of experimental and computational methods, we create an atlas of stress responses across various types of carcinomas. We find that stress responses vary within the TME and are especially active near cancer cells. Focusing on the non-immune stroma we find, across tumor types, that NRF2 and the oxidative stress response are distinctly activated in immune-regulatory cancer-associated fibroblasts and in a unique subset of cancer-associated pericytes. Our study thus provides an interactome of stress responses in cancer, offering ways to intersect survival pathways within the tumor, and advance cancer therapy.

Original languageEnglish
Article number114236
Number of pages20
JournalCell Reports
Volume43
Issue number5
Early online date17 May 2024
DOIs
Publication statusPublished - 28 May 2024

Funding

We thank the Scherz-Shouval lab members for helpful comments and insights and Reinat Nevo from the Department of Biomolecular Sciences (WIS) for assistance and advice with imaging and image analysis. We thank members of the Pietras, Ohlund, Mectha-Grigoriou, and Ostman labs for insightful discussions. This study was funded by Israel Science Foundation (ISF) grant 395- 21 and by European Research Council (ERC) grant 101043300. Publisher Copyright: © 2024 The Author(s)

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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