UPR: An Upstream Signal to EMT Induction in Cancer

© 2019 by the authors.The endoplasmic reticulum (ER) is the organelle where newly synthesized proteins enter the secretory pathway. Different physiological and pathological conditions may perturb the secretory capacity of cells and lead to the accumulation of misfolded and unfolded proteins. To relieve the produced stress, cells evoke an adaptive signalling network, the unfolded protein response (UPR), aimed at recovering protein homeostasis. Tumour cells must confront intrinsic and extrinsic pressures during cancer progression that produce a proteostasis imbalance and ER stress. To overcome this situation, tumour cells activate the UPR as a pro-survival mechanism. UPR activation has been documented in most types of human tumours and accumulating evidence supports a crucial role for UPR in the establishment, progression, metastasis and chemoresistance of tumours as well as its involvement in the acquisition of other hallmarks of cancer. In this review, we will analyse the role of UPR in cancer development highlighting the ability of tumours to exploit UPR signalling to promote epithelial-mesenchymal transition (EMT).This research was funded by the Spanish Ministerio de Economía y Competitividad (MICINN) (SAF2013-44739-R and SAF2016-76504-R, EU-FEDER funds), Instituto de Salud Carlos III (CIBERONC 16/12/00295, EU-FEDER funds), and Worldwide Cancer Research (AICR-12-1057 and WWCR-16-0295)