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Tumor Biology

, Volume 37, Issue 11, pp 14381–14390 | Cite as

Emerging tale of UPR and cancer: an essentiality for malignancy

  • Younis Mohammad Hazari
  • Arif Bashir
  • Ehtisham ul Haq
  • Khalid Majid Fazili
Review

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.

Keywords

Cancer metabolism ER stress Unfolded protein response Tumor microenvironment Hexosamine biosynthesis pathway Angiogenesis Nutrient deprivation Acidosis Hypoxia 

Abbreviations

HIF-1

Hypoxia-inducible factor 1

GCN2

General control nonderepresible 2

HBP

Hexosamine biosynthetic pathway

FGF2

Fibroblast growth factor 2

GFAT1

Glutamine:fructose-6-phosphate amidotransferase 1

VEGF

Vascular endothelial growth factor

LAMP3

Lysosomal-associated membrane protein 3

UPR

Unfolded protein response

CHOP

C/EBP (CCAAT/enhancer binding protein) homologous protein

ATF4

Activating transcription factor 4

ATF6

Activating transcription factor 6

GADD34

Growth arrest and DNA damage 34

XBP1

X-box binding protein 1

Notes

Acknowledgments

The financial support provided by grants from the DBT (No. BT/PR7240/MED/30/915/2012), DST (No. SB/SO/AS-126/2012), FIST (No. SR/FST/LSI-384/2008), SAP, and UGC (No. F.3-26/2011 (SAP-II)) facilities extended by University of Kashmir are gratefully acknowledged. Department of Science and Technology (DST) fellowship to Younis Mohammad Hazari and Department of Biotechnology (DBT) fellowship to Arif Bashir is acknowledged.

Compliance with ethical standards

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Younis Mohammad Hazari
    • 1
  • Arif Bashir
    • 1
  • Ehtisham ul Haq
    • 1
  • Khalid Majid Fazili
    • 1
  1. 1.Department of BiotechnologyUniversity of KashmirSrinagarIndia

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