Cancer Microenvironment and Endoplasmic Reticulum Stress Response

Abstract

Different stressful conditions such as hypoxia, nutrient deprivation, pH changes, or reduced vascularization, potentially able to act as growth-limiting factors for tumor cells, activate the unfolded protein response (UPR). UPR is therefore involved in tumor growth and adaptation to severe environments and is generally cytoprotective in cancer. The present review describes the molecular mechanisms underlying UPR and able to promote survival and proliferation in cancer. The critical role of UPR activation in tumor growth promotion is discussed in detail for a few paradigmatic tumors such as prostate cancer and melanoma.

Tumor stressors induce two mechanisms of intracellular P-glycoprotein–mediated resistance that are overcome by lysosomal-targeted thiosemicarbazones

“…Considering this, for the first time, we demonstrate that well known tumor stress stimuli, namely: hypoxia, nutrient starvation and ROS (12,25,26), rapidly (within 1 h) induce Pgp-re-distribution into lysosomes. This effect results in lysosomal sequestration of chemotherapeutics that are Pgp substrates.…”

“…For all experiments, to study tumor micro-environmental-induced stress, cells were exposed to either: (i) glucose starvation (0 μM) through the use of glucose-free DMEM (Cat.#: 11966-025, Life Technologies); (ii) serum starvation (no FCS); or (iii) media supplemented with H2O2 (100 μM) in the presence or absence of normoxia (21% O2), or hypoxia (1% O2). Each of these stress stimuli are well known to exist within the tumor microenvironment (12,25,26).…”

“…Classical tumor micro-environmental stressors assessed included: hypoxia (1% O2), glucose starvation (0 µM; (-) glucose), serum starvation ((-) serum), or H2O2 stress (100 μM; (+) H2O2) (12,25,26).…”

A Mini Review of Cancer Treatment and Epigenetic

“…Cancer cells act in contrast to noncancerous cells by increasing the expression of ER stress-associated proteins and a common the unfolded protein response (UPR), a phenomenon that occurs as an exacerbation of endoplasmic reticulum (ER) [29] Or UPR addiction [30] this allows the cancer cells to heavily rely on the UPR for survival in the environment within which they usually proliferate: reduced nutrients, acidosis, energy deficiency, and low oxygen tension (hypoxia) [31,32].…”

Effects of gene polymorphisms in the endoplasmic reticulum stress pathway on clinical outcomes of chemoradiotherapy in Chinese patients with nasopharyngeal carcinoma

“…ER stress may be activated by perturbation of the tumor microenvironment by factors such as hypoxia, pH changes, and oxidative stress induced by both chemotherapy and radiotherapy [15,16] . ER stress is also involved in cancer cell proliferation, cytoprotective autophagy, apoptosis, angiogenesis, and the inflammatory response mediated by the unfolded protein response (UPR), thereby resulting in cancer development and metastases [17] . Functional polymorphisms in ER stress pathway related genes, especially single nucleotide polymorphisms (SNPs) in the coding regions, may affect the expression or activity of proteins.…”