Abstract
The unfolded protein response (UPR) was originally identified as a signaling network coordinating adaptive and apoptotic responses to accumulation of unfolded proteins in the endoplasmic reticulum (ER). More recent work has shown that UPR signaling can be triggered by a multitude of cellular events and that the UPR plays a critical role in the prevention of cell transformation but also in tumor development. This has been particularly well illustrated with studies on one of the three major ER stress sensors, IRE1. This ER resident type I transmembrane protein senses luminal ER stress and transduce signals through its cytosolic RNase activity. IRE1 signaling has been shown to contribute to the progression of solid tumors through pro-angiogenic mechanisms. Herein, we expose the methodologies for investigating IRE1 signaling in tumor cells and in tumors. Moreover, we show that selective pharmacological inhibition of IRE1 RNase activity sensitizes tumor cells to ER stress.
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Acknowledgements
This work was funded by grants from INSERM, Institut National du Cancer (INCa), La Ligue Contre le Cancer to EC. S.L. was supported by a PhD scholarship from the French government, and N.D. was supported by a postdoctoral fellowship from the Fondation de France.
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Lhomond, S. et al. (2015). Adaptation of the Secretory Pathway in Cancer Through IRE1 Signaling. In: Oslowski, C. (eds) Stress Responses. Methods in Molecular Biology, vol 1292. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2522-3_13
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DOI: https://doi.org/10.1007/978-1-4939-2522-3_13
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