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Cancer

Adapting to cell stress from inside and out

Nature Cell Biology volume 21, pages 799–800 (2019)Cite this article

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The ability of cancer cells to adapt to external and internal stresses is critical for tumourigenesis. A new study now shows that the integrated stress response is critical for tumour cell adaptation to stress induced by c-MYC activation, providing mechanistic insights into tumour responses to intrinsic stresses with implications for cancer therapies.

Tumour cells must adapt to survive in harsh environments that are a consequence of expanded tumour mass and restricted vascularization. Stressful tumour environments limit the availability of nutrients and oxygen, triggering the integrated stress response (ISR), which induces translational and transcriptional modes of gene expression that serve to restore cell homeostasis1,2,3. Cancer cells also experience intrinsic stresses owing to activation of oncogenes that reprogram metabolic processes to facilitate rapid cell growth and proliferation. How do cancer cells adapt to these intrinsic stresses, and do these processes mirror adaptive pathways responding to external insults? In this issue of Nature Cell Biology, Tameire et al.4 report that the ISR is activated in tumour cells overexpressing the proto-oncogene c-MYC (MYC) by stresses afflicting the endoplasmic reticulum (ER) and the cytosol. ISR activation provides resistance to stresses induced by MYC activation, demonstrating its critical role in cellular adaptations to both cell-intrinsic stresses and environmental insults that are encountered during tumour progression.

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Fig. 1: The integrated stress response (ISR) is activated by both intrinsic and extrinsic stresses in human cancer.

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  1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Kirk A. Staschke & Ronald C. Wek

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  1. Kirk A. Staschke
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  2. Ronald C. Wek
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Correspondence to Ronald C. Wek.

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Competing interests

K.A.S. is a consultant for and receives research support from HiberCell, Inc. R.C.W. has research support from Eli Lilly and Company.

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Staschke, K.A., Wek, R.C. Adapting to cell stress from inside and out. Nat Cell Biol 21, 799–800 (2019). https://doi.org/10.1038/s41556-019-0354-x

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