Polymerase I and Transcript Release Factor Acts As an Essential Modulator of Glioblastoma Chemoresistance

Wang, Xin; Liu, Tianzhu; Bai, Yifeng; Liao, Hongzhan; Qiu, Shengcong; Chang, Zhenhua; Liu, Yanting; Yan, Xiaohui; Guo, Hongbo

doi:10.1371/journal.pone.0093439

Cited by 20 publications

(29 citation statements)

References 45 publications

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“…17,41 Movement of PgP into cholesterol rich regions or altering cholesterol content of domains containing PgP is a potential mechanism to regulate PgP activity.…”

Section: Discussionmentioning

confidence: 99%

“…16 Based on the observation that caveolar localization may influence PgP activity, 17 we tested whether caveolar proteins moved within the rat brain endothelial cells in vivo in response to PIP. Movement of caveolar proteins during PIP could indicate trafficking events directly involved with the transfer of PgP to the PM or a change in membrane microenvironment that would influence PgP activity at the PM.…”

Section: Localization Of Cav1 In Rat Brain Microvesselsmentioning

confidence: 99%

“…15 Caveolae are dynamic structures that participate in protein trafficking and regulation of signaling cascades. 16 Caveolar localization may influence PgP activity; 17 binding of caveolin1 (CAV1), a caveolar scaffold protein, to PgP has been implicated in the regulation of PgP activity. 18 Taken together, these data suggest that PgP trafficking between intracellular compartments or within membrane microdomains is a potential PgP regulatory mechanism in vivo.…”

Section: Introductionmentioning

confidence: 99%

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P-glycoprotein traffics from the nucleus to the plasma membrane in rat brain endothelium during inflammatory pain

Tome

Herndon

Schaefer

et al. 2016

J Cereb Blood Flow Metab

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P-glycoprotein (PgP), a drug efflux pump in blood-brain barrier endothelial cells, is a major clinical obstacle for effective central nervous system drug delivery. Identifying PgP regulatory pathways that can be exploited clinically is critical for improving central nervous system drug delivery. We previously found that PgP activity increases in rat brain microvessels concomitant with decreased central nervous system drug delivery in response to acute peripheral inflammatory pain. In the current study, we tested the hypothesis that PgP traffics to the luminal plasma membrane of the microvessel endothelial cells from intracellular stores during peripheral inflammatory pain. Using immunofluorescence microscopy, we detected PgP in endothelial cell nuclei and in the luminal plasma membrane in control animals. Following peripheral inflammatory pain, luminal PgP staining increased while staining in the nucleus decreased. Biochemical analysis of nuclear PgP content confirmed our visual observations. Peripheral inflammatory pain also increased endothelial cell luminal staining of polymerase 1 and transcript release factor/cavin1 and serum deprivation response protein/cavin2, two caveolar scaffold proteins, without changing caveolin1 or protein kinase C delta binding protein/cavin3 location. Our data (a) indicate that PgP traffics from stores in the nucleus to the endothelial cell luminal membrane in response to peripheral inflammatory pain; (b) provide an explanation for our previous observation that peripheral inflammatory pain inhibits central nervous system drug uptake; and (c) suggest a novel regulatory mechanism for PgP activity in rat brain. KeywordsCaveolin1, P-glycoprotein, protein kinase C delta binding protein/cavin3, polymerase 1 and transcript release factor/ cavin1, serum deprivation response protein/cavin2, trafficking

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“…17,41 Movement of PgP into cholesterol rich regions or altering cholesterol content of domains containing PgP is a potential mechanism to regulate PgP activity.…”

Section: Discussionmentioning

confidence: 99%

Section: Localization Of Cav1 In Rat Brain Microvesselsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

P-glycoprotein traffics from the nucleus to the plasma membrane in rat brain endothelium during inflammatory pain

Tome

Herndon

Schaefer

et al. 2016

J Cereb Blood Flow Metab

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“…The knock‐down of CAVIN1 reduces multidrug resistance in breast cancer cell line MCF‐7/ADR cells . In GBM, it has been shown that CAVIN1 mediated chemoresistance in U251 cell lines, and its expression was upregulated in samples from relapsed GBM patients, but the number of patient samples was limited . A recent study identified an eight‐gene signature, including CAVIN1 that could predict the outcome of GBM patients .…”

Section: Introductionmentioning

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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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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“…The pressure‐sensing capabilities of caveolae and the mechanotransduction capacities of caveola‐forming proteins have pathophysiological consequences on cardiovascular or muscle function . In glioblastoma (GBM), caveolae or caveola‐forming proteins have been proposed to be important in the regulation of EGFR signalling, resistance to treatment and exosome‐mediated cell‐cell communication . Moreover, the expression of both caveolin‐1 and CAVIN1 are increased in GBM compared to normal samples and are associated with shorter patient survival time and correlated with expression of the matrix proteases uPA and gelatinases …”

Section: Introductionmentioning

confidence: 99%

A role for caveola‐forming proteins caveolin‐1 and CAVIN1 in the pro‐invasive response of glioblastoma to osmotic and hydrostatic pressure

Qiu

Nassar

et al. 2020

J Cellular Molecular Medi

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In solid tumours, elevated interstitial fluid pressure (osmotic and hydrostatic pressure) is a barrier to drug delivery and correlates with poor prognosis. Glioblastoma (GBM) further experience compressive force when growing within a space limited by the skull. Caveolae are proposed to play mechanosensing roles, and caveola‐forming proteins are overexpressed in GBM. We asked whether caveolae mediate the GBM response to osmotic pressure. We evaluated in vitro the influence of spontaneous or experimental down‐regulation of caveola‐forming proteins (caveolin‐1, CAVIN1) on the proteolytic profile and invasiveness of GBM cells in response to osmotic pressure. In response to osmotic pressure, GBM cell lines expressing caveola‐forming proteins up‐regulated plasminogen activator (uPA) and/or matrix metalloproteinases (MMPs), some EMT markers and increased their in vitro invasion potential. Down‐regulation of caveola‐forming proteins impaired this response and prevented hyperosmolarity‐induced mRNA expression of the water channel aquaporin 1. CRISPR ablation of caveola‐forming proteins further lowered expression of matrix proteases and EMT markers in response to hydrostatic pressure, as a model of mechanical force. GBM respond to pressure by increasing matrix‐degrading enzyme production, mesenchymal phenotype and invasion. Caveola‐forming proteins mediate, at least in part, the pro‐invasive response of GBM to pressure. This may represent a novel target in GBM treatment.

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Polymerase I and Transcript Release Factor Acts As an Essential Modulator of Glioblastoma Chemoresistance

Cited by 20 publications

References 45 publications

P-glycoprotein traffics from the nucleus to the plasma membrane in rat brain endothelium during inflammatory pain

P-glycoprotein traffics from the nucleus to the plasma membrane in rat brain endothelium during inflammatory pain

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

A role for caveola‐forming proteins caveolin‐1 and CAVIN1 in the pro‐invasive response of glioblastoma to osmotic and hydrostatic pressure

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