title: Emerging tale of UPR and cancer: an essentiality for malignancy.
abstract: A set of cellular response to counter any alteration in homeostasis of a cell originating at endoplasmic reticulum is collectively termed as unfolded protein response (UPR). It initially is adaptive in nature as to restore cellular normalcy failing in course often activates pro-apoptotic signaling pathway resulting in cell death. UPR has emerged as an essential adaptation mechanism that cross talk with various cellular processes for cancer pathogenesis. Interestingly, it plays diverse role in plethora of signaling pathways instrumental in transformation, cell invasion, cell migration, metastasis, neovascularization, proliferation, and maintenance of energy metabolism of cancerous cells. In cancerous cells, it is triggered by change in microenvironment of a cell usually driven by hypoxia, acidosis, and nutrient deprivation, which often leads to positive selection pressure involving the reprogramming of energy metabolism which promotes channelization of limited metabolites into the hexosamine biosynthetic pathway (HBP). Substantial evidences suggest the role of UPR in oncogene (Myc, mTOR, RAS, HER2) driven cancer transformation and progression. In this review, we have comprehensively underlined the role played by UPR in adaptation, transformation, proliferation, invasion, and metastasis of cancerous cells.
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India.
authors.forename: Younis Mohammad
authors.initials: YM
authors.lastname: Hazari
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India.
authors.forename: Arif
authors.initials: A
authors.lastname: Bashir
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India.
authors.forename: Ehtisham Ul
authors.initials: EU
authors.lastname: Haq
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India. fazili@kashmiruniversity.ac.in.
authors.forename: Khalid Majid
authors.initials: KM
authors.lastname: Fazili
mesh_terms: D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology*
keywords: Acidosis; Angiogenesis; Cancer metabolism; ER stress; Hexosamine biosynthesis pathway; Hypoxia; Nutrient deprivation; Tumor microenvironment; Unfolded protein response