Identification of the Transmembrane Glucose Regulated Protein 78 as a Biomarker for the Brain Cancer Glioblastoma Multiforme by Gene Expression and Proteomic Studies.

Hn, Banerjee; Hyman, Gwyn; Evans, Shavonda; Manglik,; Gwebu, Ephraim T.; A, Banerjee; Vaughan, Deirdre; Medley, Jewe; Krauss, Christopher; Wilkins, James A.; Smith, Stacy; Banerji, A. K.; Rousch, Jeffrey M.

doi:10.4172/2155-9589.1000126

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…immunoblotting, and proteomic approaches in patient samples (10,33,34). These data suggest a chronic activation of the UPR and GRP78 activity within GBM cells.…”

Section: Grp78 In Glioblastoma and Its Role In Resistance Grp78 In Gbmentioning

confidence: 78%

Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

Liu¹,

Tsung²,

Attenello³

2020

Front. Oncol.

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Glioblastoma (GBM) is the most common primary brain tumor, carrying a very poor prognosis, with median overall survival at about 12 to 15 months despite surgical resection, chemotherapy with temozolomide (TMZ), and radiation therapy. GBM recurs in the vast majority of patients, with recurrent tumors commonly displaying increase in resistance to standard of care chemotherapy, TMZ, as well as radiotherapy. One of the most commonly cited mechanisms of chemotherapeutic and radio-resistance occurs via the glucose-regulated protein 78 (GRP78), a well-studied mediator of the unfolded protein response (UPR), that has also demonstrated potential as a biomarker in GBM. Overexpression of GRP78 has been directly correlated with malignant tumor characteristics, including higher tumor grade, cellular proliferation, migration, invasion, poorer responses to TMZ and radiation therapy, and poorer patient outcomes. GRP78 expression is also higher in GBM tumor cells upon recurrence. Meanwhile, knockdown or suppression of GRP78 has been shown to sensitize cells to TMZ and radiation therapy. In light of these findings, various novel developing therapies are targeting GRP78 as monotherapies, combination therapies that enhance the effects of TMZ and radiation therapy, and as treatment delivery modalities. In this review, we delineate the mechanisms by which GRP78 has been noted to specifically modulate glioblastoma behavior and discuss current developing therapies involving GRP78 in GBM. While further research is necessary to translate these developing therapies into clinical settings, GRP78-based therapies hold promise in improving current standard-of-care GBM therapy and may ultimately lead to improved patient outcomes.

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“…immunoblotting, and proteomic approaches in patient samples (10,33,34). These data suggest a chronic activation of the UPR and GRP78 activity within GBM cells.…”

Section: Grp78 In Glioblastoma and Its Role In Resistance Grp78 In Gbmentioning

confidence: 78%

Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

Liu¹,

Tsung²,

Attenello³

2020

Front. Oncol.

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“…At the same time, we now know that this protein plays crucial roles in GB proliferation, resistance, metastasis, and angiogenesis in hypoxic cellular environments characterized by glucose deprivation and inflammatory responses, among other factors that induce its expression. In other words, GRP78 can facilitate the adaptation of tumoral cells and promote their growth in an anoxic environment [21,22].…”

Section: Current Perspectives For the Treatment Of Glioblastoma (Gb) ...mentioning

confidence: 99%

Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses

García-López,

Zaragoza-Ojeda,

Eguía-Aguilar

et al. 2024

IJMS

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The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

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Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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Identification of the Transmembrane Glucose Regulated Protein 78 as a Biomarker for the Brain Cancer Glioblastoma Multiforme by Gene Expression and Proteomic Studies.

Cited by 4 publications

References 23 publications

Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

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