Crosstalk between Endoplasmic Reticulum Stress, Unfolded Protein Response (UPR) and Wnt Signaling Pathway in Cancer

Context: Endoplasmic reticulum stress (ER stress) is associated with endoplasmic reticulum perturbation homeostasis. Prolonged ER stress conditions may induce cell death. Unfolded protein response (UPR) attempts to restore normal cell conditions. Evidence Acquisition: There now exists an emergent body of evidence identifying the WNT signaling network as a regulator of cancer cell metabolism. Given that existing findings show that the WNT pathway and ER stress regulates changes in metabolic activities of cancer cells suggesting these signaling pathways represent critical nodes in the regulation of central metabolism in tumors. Results: Findings suggest that the molecular cross-talks between hypoxic ER stresses, Wnt/βcatenin signaling, may represent an important mechanism that enables some tumor subtypes to survival and grow in hypoxic conditions. Conclusions: The present article disuses differential effects of the activation of the three arms of UPR, namely endoplasmic reticulum kinase (PERK), activation transcription factor -6 (ATF-6), and inositol –requiring enzyme (IRE-1) on cancer. This review also highlights regulators and downstream effectors of Wnt cascade and addresses the increasingly apparent crosstalk of Wnt with other tumorigenic signaling pathways.