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Emerging tale of UPR and cancer: an essentiality for malignancy

  • Review
  • Published:
Tumor Biology

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.

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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

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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.

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  1. Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India

    Younis Mohammad Hazari, Arif Bashir, Ehtisham ul Haq & Khalid Majid Fazili

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  1. Younis Mohammad Hazari
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  2. Arif Bashir
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  3. Ehtisham ul Haq
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  4. Khalid Majid Fazili
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Correspondence to Khalid Majid Fazili.

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Hazari, Y.M., Bashir, A., Haq, E.u. et al. Emerging tale of UPR and cancer: an essentiality for malignancy. Tumor Biol. 37, 14381–14390 (2016). https://doi.org/10.1007/s13277-016-5343-0

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  • DOI: https://doi.org/10.1007/s13277-016-5343-0

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