Endoplasmic Reticulum Stress and the Hallmarks of Cancer

Hery Urra (1, 2, 3) , Estefanie Dufey (1, 2, 3) , Tony Avril (4, 5) , Eric Chevet (4, 5) , Claudio Hetz (6, 2, 3, 1)

1 USACH - Universidad de Santiago de Chile [Santiago]
2 Biomedical Neuroscience Institute
3 Institute of Biomedical Sciences
4 OSS - Oncogenesis Stress Signaling
5 CRLCC - CRLCC Eugène Marquis
6 Department of Immunology and Infectious Diseases

Tumor cells are often exposed to intrinsic and external factors that alter protein homeostasis, thus producing endoplasmic reticulum (ER) stress. To cope with this, cells evoke an adaptive mechanism to restore ER proteostasis known as the unfolded protein response (UPR). The three main UPR signaling branches initiated by IRE1α, PERK, and ATF6 are crucial for tumor growth and aggressiveness as well as for microenvironment remodeling or resistance to treatment. We provide a comprehensive overview of the contribution of the UPR to cancer biology and the acquisition of malignant characteristics, thus highlighting novel aspects including inflammation, invasion and metastasis, genome instability, resistance to chemo/radiotherapy, and angiogenesis. The therapeutic potential of targeting ER stress signaling in cancer is also discussed.

Mots clés: Cancer; ER stress; IRE1α; UPR; XBP1

Domaines: Sciences du Vivant [q-bio]; Cancer

Hery Urra, Estefanie Dufey, Tony Avril, Eric Chevet, Claudio Hetz. Endoplasmic Reticulum Stress and the Hallmarks of Cancer. Trends in Cancer, 2016, 2 (5), pp.252-262. ⟨10.1016/j.trecan.2016.03.007⟩. ⟨hal-01308007⟩