Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential
Reads0
Chats0
TLDR
The glucose-regulated proteins are found and regulation are described, as well as their biological functions in cancer and promising agents that use or target the GRPs are developed, and their efficacy as anticancer therapeutics is discussed.Abstract:
The glucose-regulated proteins (GRPs) are stress-inducible chaperones that mostly reside in the endoplasmic reticulum or the mitochondria. Recent advances show that the GRPs have functions that are distinct from those of the related heat shock proteins, and they can be actively translocated to other cellular locations and assume novel functions that control signalling, proliferation, invasion, apoptosis, inflammation and immunity. Mouse models further identified their specific roles in development, tumorigenesis, metastasis and angiogenesis. This Review describes their discovery and regulation, as well as their biological functions in cancer. Promising agents that use or target the GRPs are being developed, and their efficacy as anticancer therapeutics is also discussed.read more
Citations
More filters
Journal ArticleDOI
Emerging applications of metabolomics in drug discovery and precision medicine
TL;DR: This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases, the growing role of metabolites in drug discovery and its potential effect on precision medicine.
Journal ArticleDOI
Endoplasmic Reticulum Stress and the Hallmarks of Cancer
TL;DR: A comprehensive overview of the contribution of the UPR to cancer biology and the acquisition of malignant characteristics is provided, thus highlighting novel aspects including inflammation, invasion and metastasis, genome instability, resistance to chemo/radiotherapy, and angiogenesis.
Journal ArticleDOI
HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells.
TL;DR: It is shown that heatshock 70-kDa protein 5 (HSPA5) negatively regulates ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells, and a potential therapeutic strategy for overcoming gemcitabine resistance is suggested.
Journal ArticleDOI
Endocrine resistance in breast cancer--An overview and update.
TL;DR: This review explores the basic mechanisms of resistance to endocrine therapies, concluding with some new insights from systems biology approaches further implicating autophagy and the UPR in detail, and a brief discussion of exciting new avenues and future prospects.
Journal ArticleDOI
Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis.
Genyuan Zhu,Amy S. Lee +1 more
TL;DR: This review highlights recent progress towards the understanding of the role of the UPR and two major GRPs in regulating homeostasis of organs arising from the endoderm, mesoderm and ectoderm.
References
More filters
Journal ArticleDOI
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.
Journal ArticleDOI
The unfolded protein response: controlling cell fate decisions under ER stress and beyond
TL;DR: Insight is provided into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6).
Journal ArticleDOI
XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response
TL;DR: It is suggested that the IRE1/XBP-1 pathway is required for efficient protein folding, maturation, and degradation in the ER and imply the existence of subsets of UPR target genes as defined by their dependence on XBP- 1.
Journal ArticleDOI
Autophagy Suppresses Tumorigenesis through Elimination of p62
Robin Mathew,Cristina M. Karp,Brian Beaudoin,Brian Beaudoin,Nhan Vuong,Guanghua Chen,Hsin-Yi Chen,Kevin Bray,Anupama Reddy,Gyan Bhanot,Céline Gélinas,Céline Gélinas,Robert S. DiPaola,Vassiliki Karantza-Wadsworth,Eileen White +14 more
TL;DR: Defective autophagy is a mechanism for p62 upregulation commonly observed in human tumors that contributes directly to tumorigenesis likely by perturbing the signal transduction adaptor function of p62-controlling pathways critical for oncogenesis.
Journal ArticleDOI
An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein.
Sean Munro,Hugh R.B. Pelham +1 more
TL;DR: A cDNA clone is characterized that encodes a protein related to the 70 kd heat shock protein, but is expressed in normal rat liver, and it is identical with two previously described proteins: GRP78, whose synthesis is induced by glucose starvation, and BiP, which is found bound to immunoglobulin heavy chains in pre-B cells.
Related Papers (5)
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more