Learn More
The endoplasmic reticulum (ER) has emerged as a major site of cellular homeostasis regulation, particularly in the unfolded protein response, which is being found to play a major role in cancer and many other diseases. Here, we address ER-mediated signaling and regulations in the context of environmental challenges in cancer, such as hypoxia, angiogenesis,(More)
BACKGROUND Amifostine (WR-2721, delivered as Ethyol) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active(More)
Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α(More)
Inositol-requiring enzyme 1 (IRE1) is a proximal endoplasmic reticulum (ER) stress sensor and a central mediator of the unfolded protein response. In a human glioma model, inhibition of IRE1alpha correlated with down-regulation of prevalent proangiogenic factors such as VEGF-A, IL-1beta, IL-6, and IL-8. Significant up-regulation of antiangiogenic gene(More)
The endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory and transmembrane proteins. ER homeostasis is often perturbed in tumor cells because of dramatic changes in the microenvironment of solid tumors, thereby leading to the activation of an adaptive mechanism named the unfolded protein response (UPR). The(More)
When endoplasmic reticulum (ER) homeostasis is perturbed, an adaptive mechanism is triggered and named the unfolded protein response (UPR). Thus far, three known UPR signaling branches (IRE-1, PERK, and ATF-6) mediate the reestablishment of ER functions but can also lead to apoptosis if ER stress is not alleviated. However, the understanding of the(More)
Tumor ischemia participates in angiogenesis and cancer progression through cellular responses to hypoxia and nutrient deprivation. However, the contribution of amino acids limitation to this process remains poorly understood. Using serum-free cell culture conditions, we tested the impact of L-glutamine deprivation on metabolic and angiogenic responses in(More)
In solid tumors, cancer cells subjected to ischemic conditions trigger distinct signaling pathways contributing to angiogenic stimulation and tumor development. Characteristic features of tumor ischemia include hypoxia and glucose deprivation, leading to the activation of hypoxia-inducible factor-1-dependent signaling pathways and to complex signaling(More)
Our aim was to explore the nutritional consequences of functional variations in the hypothalamic-pituitary-adrenocortical (HPA) axis in rats. We first aimed to compare the HPA axis activity and reactivity to stress between Fischer 344 (F344) and LOU/C (LOU) strains that differ in food behavior and metabolism. When compared with F344 rats, LOU rats showed(More)