Related Experiment Video

Updated: Mar 9, 2026

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
09:17

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma

Published on: September 13, 2022

2.8K

The unfolded protein response in glioblastomas: targetable or trouble?

Michael W Graner1

  • 1University of Colorado Denver (Anschutz Medical Campus), Aurora, CO 80045, USA.

Future Science OA
|December 30, 2016
PubMed

Insights

Glioblastomas hijack the unfolded protein response (UPR) for uncontrolled growth, leading to invasive and treatment-resistant tumors. Targeting the UPR

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Glioblastomas are aggressive brain tumors with poor outcomes.
  • Tumor cells exhibit high invasiveness, proliferation, and therapeutic resistance.
  • The unfolded protein response (UPR) is a cellular stress pathway originating in the endoplasmic reticulum (ER).

Approach:

  • This analysis explores how glioblastomas co-opt the UPR.
  • Investigates UPR's role in enhanced protein and lipid synthesis.
  • Examines UPR's contribution to tumor invasiveness, angiogenesis, and resistance.

Key Points:

  • Glioblastomas exploit the UPR to sustain high protein production and lipid biosynthesis.
  • UPR activation facilitates tumor cell proliferation, invasion, and extracellular matrix remodeling.
  • The UPR contributes significantly to glioblastoma's resistance to chemotherapy and radiotherapy.

Conclusions:

  • The UPR, particularly its chaperoning functions, represents a promising therapeutic target for glioblastoma.
  • Targeting UPR-mediated pathways may overcome treatment resistance.
  • Potential therapeutic strategies and their challenges warrant further investigation.
Keywords:
HSP90 inhibitorsbrain tumorchaperoneclinical trialglioblastomaglucose-regulated proteinsheat shock proteins

More Related Videos

Translational Orthotopic Models of Glioblastoma Multiforme07:37

Translational Orthotopic Models of Glioblastoma Multiforme

Published on: February 17, 2023

3.9K
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells12:52

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Published on: November 28, 2015

16.6K

Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
5.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K