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The UPRising connection between endoplasmic reticulum stress and the tumor microenvironment
Hery Urra1, Raúl Aravena2, Lucas González-Johnson3
1Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile.
None:
The tumor microenvironment (TME) represents a dynamic network of cancer cells, stromal cells, immune mediators, and extracellular matrix components, crucial for cancer progression. Stress conditions such as oncogene activation, nutrient deprivation, and hypoxia disrupt the endoplasmic reticulum (ER), activating the unfolded protein response (UPR), the main adaptive mechanism to restore ER function. The UPR regulates cancer progression by engaging cell-autonomous and cell-non-autonomous mechanisms, reprogramming the stroma and promoting immune evasion, angiogenesis, and invasion. This review explores the role of UPR beyond cancer cells, focusing on how ER stress signaling reshapes the TME, supporting tumor growth. The therapeutic potential of targeting the UPR is also discussed.
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