Signal Peptide Peptidase, Encoded by <i><scp>HM</scp>13</i>, Contributes to Tumor Progression by Affecting <scp>EGFR</scp>v<scp>III</scp> Secretion Profiles in Glioblastoma

Wei, Jianwei; Cai, Jinquan; Fang, Chuan; Tan, Yanli; Huang, Kai; Yang, Chao; Chen, Qun; Jiang, Chuanlu; Kang, Chunsheng

doi:10.1111/cns.12672

Cited by 29 publications

(33 citation statements)

References 28 publications

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“…IDH1 , MGMT , and EGFR are three well‐known genes that have important impacts on the survival of GBM patients and their treatment response . Based on these observations, we tested the role of CAVIN1 in the prediction of GBM patient outcome with differential IDH1 and EGFR mutation status and MGMT promoter methylation status.…”

Section: Resultssupporting

confidence: 90%

“…IDH1, MGMT, and EGFR are three well-known genes that have important impacts on the survival of GBM patients and their treatment response. [47][48][49][50] Based on these observations, we tested the role of CAVIN1 in the prediction of GBM patient outcome with differential IDH1 and EGFR mutation status and MGMT promoter methylation status. The samples were stratified according to the median value of CAVIN1 mRNA expression combined with IDH1 mutation, MGMT promoter methylation, or EGFR mutation status.…”

Section: Higher Cavin1 Expression With Idh1 and Egfr Mutations Implmentioning

confidence: 99%

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Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

et al. 2018

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Summary Aims Glioblastoma (GBM) is a lethal disease of the central nervous system with high mortality, and novel therapeutic targets and strategies for GBM are urgently needed. Caveolae‐associated protein 1 (CAVIN1) is an essential caveolar component‐encoding gene and has been poorly studied in glioma. To this end, in this study, we evaluated CAVIN1 expression in glioma tissue as well as the correlation between CAVIN1 expression and prognosis in glioma patients using the data collected from clinical samples or from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, and Gene Expression Omnibus (GEO) data sets. Methods Survival analysis was performed with the Kaplan‐Meier curve and log‐rank test. The predictive role of CAVIN1 in progressive malignancy in glioma was evaluated by using a receiver operator characteristic (ROC) curve. Gene ontology (GO), Gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) methods were used to interpret the functions of CAVIN1 in GBM. Results CAVIN1 expression was elevated in GBM compared with that in low‐grade glioma and nontumor brain samples and was correlated with unfavorable outcomes in glioma patients. Additionally, CAVIN1 could serve as an independent predictive factor for progressive malignancy in GBM. Furthermore, CAVIN1 was associated with disrupted angiogenesis and immune response in the tumor microenvironment of GBM. Conclusions We identified CAVIN1 as a prognostic biomarker and potential target for developing novel therapeutic strategies against GBM.

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Section: Resultssupporting

confidence: 90%

Section: Higher Cavin1 Expression With Idh1 and Egfr Mutations Implmentioning

confidence: 99%

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

et al. 2018

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“…We obtained paraffin‐embedded glioma tissues from patients who provided informed consent under an Institutional Ethics Committee‐approved study from the Second Affiliated Hospital of Harbin Medical University. The immunohistochemistry (IHC) assay was carried out according to our previous research . The slices were incubated with primary antibodies Galectin‐1 (CST, 1:250), VEGFA (BOTSER, 1:200), CCL2 (Proteintech, 1:100), TGF‐β (abcam, 1:100), CD68 (BOTSER, 1:50), CD163 (Proteintech, 1:50) and CD11b (CST, 1:200).…”

Section: Methodsmentioning

confidence: 99%

Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma

Chen

Han

Meng

et al. 2019

Intl Journal of Cancer

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Mutualistic and dynamic communication between tumour cells and the surrounding microenvironment accelerates the initiation, progression, chemoresistance and immune evasion of glioblastoma (GBM). However, the immunosuppressive mechanisms of GBM has not been thoroughly elucidated to date. We enrolled six microenvironmental signatures to identify glioma microenvironmental genes. The functional enrichment analysis such as ssGSEA, ESTIMATE algorithm, Gene Ontology, Pathway analysis is conducted to discover the potential function of microenvironmental genes. In vivo and in vitro experiments are used to verify the immunologic function of LGALS1 in GBM. We screen eight glioma microenvironmental genes from glioma databases, and discover a key immunosuppressive gene (LGALS1 encoding Galectin‐1) exhibiting obviously prognostic significance among glioma microenvironmental genes. Gliomas with different LGALS1 expression have specific genomic variation spectrums. Immunosuppression is a predominate characteristic in GBMs with high expression of LGALS1. Knockdown of LGALS1 remodels the GBM immunosuppressive microenvironment by down regulating M2 macrophages and myeloid‐derived suppressor cells (MDSCs), and inhibiting immunosuppressive cytokines. Our results thus implied an important role of microenvironmental regulation in glioma malignancy and provided evidences of LGALS1 contributing to immunosuppressive environment in glioma and that targeting LGALS1 could remodel immunosuppressive microenvironment of glioma.

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“…This has so far only been investigated for SPP. SPP is strongly upregulated in several types of cancer including breast, colon and lung tumours [95] as well as glioblastoma multiforme (GBM) [96]. In many cases, expression of SPP correlates with the progression and malignancy of the tumour [95,96] making it a potential biomarker for staging of these diseases.…”

Section: Cancermentioning

confidence: 99%

“…SPP is strongly upregulated in several types of cancer including breast, colon and lung tumours [95] as well as glioblastoma multiforme (GBM) [96]. In many cases, expression of SPP correlates with the progression and malignancy of the tumour [95,96] making it a potential biomarker for staging of these diseases. While in some cases the pro-tumorigenic function of SPP could be delineated to processing of individual substrates like HO-1 [51] or FKBP8 [95], the molecular mechanism underlying the pro-tumorigenic function of SPP in EGFRvIII glioblastoma is not as well understood.…”

Section: Cancermentioning

confidence: 99%

Physiological functions of SPP/SPPL intramembrane proteases

Mentrup

Cabrera-Cabrera

Fluhrer

et al. 2020

Cell. Mol. Life Sci.

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Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still growing spectrum of biological functions and also promoted the substrate discovery of these proteases. In this review, we will summarise the current hypotheses how phenotypes of these mouse models are linked to the molecular function of the enzymes. At the cellular level, SPP/SPPL-mediated cleavage events rather provide specific regulatory switches than unspecific bulk proteolysis. By this means, a plethora of different cell biological pathways is influenced including signal transduction, membrane trafficking and protein glycosylation.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Signal Peptide Peptidase, Encoded by HM13, Contributes to Tumor Progression by Affecting EGFRvIII Secretion Profiles in Glioblastoma

Abstract: Collectively, our study identifies that SPP affects EGFRvIII secretion profiles and thus promotes tumor progression, providing further understanding of the formation of secreted vesicles and driving role of EGFRvIII in GBM.

Cited by 29 publications

References 28 publications

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma

Physiological functions of SPP/SPPL intramembrane proteases

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