Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets
Abstract
:1. Glioblastoma
1.1. Diagnosis
1.2. Pathogenesis
1.3. Standard of Care
2. Protein Quality Control
2.1. Containment by Heat Shock Protein 70
2.2. Direction by BCL2-Associated Anthogenes
2.3. Degradation by the Ubiquitin Proteasome System
2.4. Degradation by the Autophagic–Lysosomal Pathway
3. Glioblastoma as a Proteinopathy
3.1. Cancer and the Common Cascade
3.2. Cancer and the Directional Proteins
3.3. Cancer and the Ubiquitin Proteasome System
3.4. Cancer and the Autophagy–Lysosome Pathway
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AIF | apoptosis-inducing factor |
AKT | Ak strain transforming kinase |
ALP | autophagic–lysosomal pathway |
ATF4 | activating transcription factor 4 |
BAG | BCL2-associated anthogene |
Bag | BAG protein |
BRAF | rapidly accelerated fibrosarcoma homolog B |
CMA | chaperone-mediated autophagy |
DNA | deoxyribonucleic acid |
EGFR | epidermal growth factor receptor |
eIF2α | translation initiation factor 2α |
GBM | glioblastoma |
HOX5A | homeobox A5 |
HSF1 | heat shock factor 1 |
HSP70 | heat shock protein 70 kD |
IDH | isocitrate dehydrogenase |
LAMP2A | lysosome-associated membrane protein |
MET | Mesenchymal–epithelial transition factor receptor |
MGMT | O6-methylguanine–DNA methyltransferase |
mTOR | mammalian target of rapamycin |
miRNA | micro-ribonucleic acid |
mRNA | messenger ribonucleic acid |
MVP | microvascular proliferation |
NLS | nuclear location sequence |
PDGFA | Platelet-derived growth factor A |
PERK | RNA-like endoplasmic reticular kinase |
PQC | protein quality control |
PTEN | phosphatase and tensin homolog |
Ras | rat sarcoma |
r-HSP7 | spastic paraplegia type 7 |
SBD | Substrate-binding domain |
SMAD3/4 | small mothers against decapentaplegic homolog 3/4 |
SNP | Single-nucleotide polymorphisms |
TCGA | The Cancer Genome Atlas |
TFEB | transcription factor EB |
TERT | telomerase elongation reverse transcriptase |
WHO | World Health Organization |
Wnt | wingless integrated homolog |
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Mutation | Prevalence | Impact |
---|---|---|
Ras proliferation | 88% | Mitosis |
EGFR * | 45% | Amplification of growth receptor |
PTEN * | 36% | Deletion of P13K inhibitor |
NF1 | 23% | Silencing/deletion of Ras suppressor |
PI3K | 15% | PI3K gain of function |
PDGFRA * | 13% | Amplification of growth receptor |
p53 tumor suppression | 87% | Persistence of oncogenes |
ARF | 49% | Deletion of p53 dis-inhibitor |
p53 | 35% | p53 silencing/deletion |
MDM2 | 14% | Amplification of p53 suppressor |
Rb tumor suppression | 78% | Disinhibition of G1/S progression |
CDK N2A | 52% | Deletion of Rb dis-inhibitor |
CDK N2B | 47% | Deletion of Rb dis-inhibitor |
CDK4 | 18% | Amplification of Rb inhibitor |
Rb | 11% | Deletion of Rb |
Study | Biopsy Source | Outcome |
---|---|---|
Bag1 | ||
Aveic et al., 2011 [96] | Pediatric bone marrow | Bag1 protein is required for acute myeloid lymphoma cell survival. |
Bai et al., 2007 [97] | Colon carcinoma | Bag1 gene expression is strongly associated with metastasis, shorter survival, and advanced staging of colon cancer. |
D’Arcangelo et al., 2018 [98] | Melanoma and nevi (HPA) | Bag1 gene and protein expression are diagnostic for melanoma, with levels differentiating malignant and benign nevi. |
Du et al., 2021 [99] | Breast cancer (TCGA) | Bag1 gene expression is prognostic for severity and outcomes of breast cancer. |
Gennaro et al., 2019 [100] | Osteosarcoma * | Isoform Bag1S inhibits MYC-induced apoptosis, promoting cancer cell survival. |
Mariotto et al., 2021 [101] | B-cell acute lymphoblastic lymphoma (Zebrafish) | Bag1 is prognostic for severity and outcomes of B-ALL. Bag1 inhibitor Thio-2 induces cytotoxicity as a sole therapy and increases the pro-apoptotic effects of other B-ALL therapies. |
Wu et al., 2021 [102] | Renal clear cell carcinoma (TCGA) | Bag1 is prognostic for severity and outcomes of RCCC. |
Bag2 | ||
Hong et al., 2018 [103] | Esophageal squamous cell carcinoma (TCGA) | Bag2 overexpression is predictive of poor survival outcomes in ESCC. |
Esophageal squamous cell carcinoma * | Bag2 knock-out inhibits ESCC proliferation. | |
Sun et al., 2020 [104] | Gastric cancer (HPA) | Bag2 protein levels correlate with gastric cancer prognosis. |
Gastric cancer * | Bag2 enhances proliferation and metastasis of tumor cells. | |
Yue et al., 2015 [105] | Bone, liver, colorectal, breast, and lung cancers * | Bag2 maintains mutant p53, increasing its gain-of-function cell growth, metastasis, and treatment resistance. |
Zhang et al., 2021 [106] | Hepatocellular carcinoma | Bag2 is significantly upregulated in HCC, with higher levels correlating with shorter survival. |
Hepatocellular carcinoma * | Silencing of Bag2 facilitated apoptotic intervention, improving HCC treatments. | |
Bag3 | ||
Shi et al., 2018 [107] | Chondrosarcoma | Bag3 expression is significantly increased in malignant chondrosarcoma compared to normal cartilage and benign tumors. |
Lee et al., 2019 [108] | Gastric cancer | Bag3 is upregulated in response to hepatocyte growth factor, increasing cancer resistance, proliferation, and invasion. |
Li et al., 2018 [109] | Colorectal cancer | Bag3 levels correlate with patient gender and tumor size. |
Colorectal cancer * | Bag3 gene knock-out impairs proliferation, metastasis, and chemoresistance of colorectal cancer cells. | |
Linder et al., 2022 [110] | Glioblastoma * | Bag3 inhibits ciliogenesis, increasing GBM aggression and treatment resistance. |
Wang & Tian, 2018 [111] | Cervical cancer | Inhibition of Bag3 halts cell proliferation and metastatic invasion of cervical cancer. |
Yunoki et al., 2015 [112] | Retinoblastoma * | Bag3 protects retinoblastoma cells from apoptosis in the setting of heat stress. |
Bag4 | ||
Du et al., 2015 [113] | Hepatocellular carcinoma * | Bag4 expression increases proliferation and survival of liver cancer cells. |
Jhang et al., 2021 [114] | Gastric cancer | Bag4 expression levels correlate with stage, metastasis, tumor size, and outcomes in patients with gastric cancer. |
Rho et al., 2018 [115] | Blood plasma pre- and post-diagnosis of colon cancer | Bag4 elevation can be used in an early-detection biomarker panel for the screening/diagnosis of colon cancer. |
Bag5 | ||
Bi et al., 2016 [116] | Ovarian cancer * | Bag5 is tumorigenic in epithelial ovarian cancer with Bag5 knock-down improving the effect of tumor-suppression therapy. |
Bruchmann et al., 2013 [117] | Prostate cancer | Bag5 is overexpressed in prostate cancer with stress-induced migration to the ER inhibiting apoptosis. |
Che et al., 2021 [118] | Hepatocellular carcinoma | Endogenous Bag5 inhibitor PRMT 6 (protein arginine N-methyltransferase 6) is decreased in HCC, disinhibiting Bag5, stabilizing HSP70, & increasing pro-survival ALP. |
Hepatocellular carcinoma * | Suppression of Bag5 leads to instability of HSP70, increasing cell susceptibility to anti-cancer agents (i.e., sorafenib). | |
Wang et al., 2021 [119] | Ovarian tissue following cisplatin trial | Bag5 knockdown contributes to the metabolism shift of cancer development. Bag5 is increased treatment-sensitive ovarian cancer. |
Yan et al., 2021 [120] | Hepatocellular carcinoma * | Bag5 expression promotes hepatocellular oncogenesis. |
Zhang et al., 2020 [121] | Papillary thyroid cancer * | Bag5 is overexpressed in papillary thyroid cancer & is requisite for invasion & metastasis. |
Bag6 | ||
Ragimbeau et al., 2021 [122] | Colon cancer * | Bag6 protein is requisite for colon cancer cells to proliferate. |
Schuldner et al., 2019 [123] | Melanoma * | The Bag6-p53 pathway is requisite for pro-oncogenic exosome formation. |
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Rocchi, A.; Wollebo, H.S.; Khalili, K. Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets. Int. J. Mol. Sci. 2022, 23, 9734. https://doi.org/10.3390/ijms23179734
Rocchi A, Wollebo HS, Khalili K. Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets. International Journal of Molecular Sciences. 2022; 23(17):9734. https://doi.org/10.3390/ijms23179734
Chicago/Turabian StyleRocchi, Angela, Hassen S. Wollebo, and Kamel Khalili. 2022. "Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets" International Journal of Molecular Sciences 23, no. 17: 9734. https://doi.org/10.3390/ijms23179734