Lack of glutathione peroxidase-8 in the ER impacts on lipid composition of HeLa cells microsomal membranes

Bosello-Travain, Valentina; Miotto, Giovanni; Vučković, Ana-Marija; Cozza, Giorgio; Roveri, Antonella; Toppo, Stefano; Ursini, Fulvio; Venerando, Rina; Zaccarin, Mattia; Maiorino, Matilde

doi:10.1016/j.freeradbiomed.2019.12.010

Cited by 13 publications

(9 citation statements)

References 39 publications

(62 reference statements)

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“…Finding novel and potent biomarkers is a key step for investigating targeted therapy. GPX8 as a member of the GPX family plays an important role in protecting cells against oxidative stress [ 11 ]. Moreover, several reports indicated GPX8 dysregulation in gastric cancers through bioinformatics analysis [ 12 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…GPX3 hypermethylation has been found in gastric cancer, which is associated with tumor recurrence in gastric cancer patients over 60 years old [ 10 ]. GPX8, as a unique GPX, is located in the membranes of ER (endoplasmic reticulum) and prevent the spill of hydrogen peroxide to control redox status [ 11 ]. Dysregulation of GPX8 has been found in several tumors such as gastric cancer [ 12 – 14 ], but its molecular mechanism in gastric cancer has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

Chen

Shan

et al. 2020

Cancer Cell Int

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Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

Chen

Shan

et al. 2020

Cancer Cell Int

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“…GPX8 has multifarious functions in the body, which have been illustrated in recent studies. For example, GPX8 protects against endotoxic shock ( Hsu et al, 2020 ), regulates oxidative stress during pregnancy ( Mihalik et al, 2020 ), and maintains microsomal membrane lipid homeostasis in HELA cells ( Bosello-Travain et al, 2020 ). In addition, GPX8 has also been found to promote tumor progression through multiple important pathways, such as Wnt and JAK/STAT3 ( Chen et al, 2020 ; Khatib et al, 2020 ; Zhang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The overexpression of GPX8 is correlated with poor prognosis in GBM patients

Jiang

Guan

et al. 2022

Front. Genet.

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Glutathione peroxidase 8 (GPX8), located in the endoplasmic reticulum, is associated with poor prognosis in several cancers. However, the expression and functions of GPX8 in cancers remain unclear. The purpose of this study was to explore the expression and functions of GPX8 in glioblastoma (GBM). We obtained expression data of GPX8 by accessing the TCGA, CGGA, GEPIA, and TIMER2.0 databases and validated them using western blot and immunohistochemistry. The Kaplan–Meier overall survival curve and Cox regression model were used to evaluate the prognostic value of GPX8 in glioma patients. Gene ontology (GO) and function enrichment analysis were used to investigate the potential function of GPX8 in GBM. Correlation analysis was used to clarify the role of GPX8 in proneural–mesenchymal transition (PMT). We studied the correlation between GPX8 expression and GBM immune infiltration by accessing cBioPortal and TIMER2.0 databases. Here, we demonstrated that GPX8 was significantly upregulated in GBM, and was associated with IDH-wildtype and mesenchymal subtype with poor prognosis. Survival analysis results indicated that GPX8 is an independent prognostic factor for overall survival (OS) in all WHO-grade glioma patients. Through the functional studies, we found that high expression of GPX8 correlated with mesenchymal signature and negatively correlated with proneural signature, indicating that GPX8 might promote PMT in GBM. Finally, based on correlation analysis, we found that the expression of GPX8 was associated with immune infiltration and the IL1/MYD88/IRAK/NF-κB pathway in GBM. Our results show that GPX8 is a key factor affecting the prognosis of GBM patients, and its targeting has the potential to provide a novel therapeutic approach.

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“…Glutathione peroxidase 8 is a scavenger of ER-derived H 2 O 2 [210]. Knockdown of this enzyme increases CERT expression, along with a decreased ceramide level and an increased sphingomyelin level in HeLa cells [211]. Meanwhile, the polyunsaturated fatty acid (PUFA) content in phospholipids is decreased, as an adaptive mechanism leading to phospholipid-enriched membranes less prone to oxidative stress [211] and more resistant to free radicals and chemotherapies in cancer cells [212].…”

Section: Oxidative Stressmentioning

confidence: 99%

Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer

Chung

Liu

et al. 2021

IJMS

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Sphingolipids are a class of essential lipids implicated in constructing cellular membranes and regulating nearly all cellular functions. Sphingolipid metabolic network is centered with the ceramide–sphingomyelin axis. Ceramide is well-recognized as a pro-apoptotic signal; while sphingomyelin, as the most abundant type of sphingolipids, is required for cell growth. Therefore, the balance between these two sphingolipids can be critical for cancer cell survival and functioning. Ceramide transfer protein (CERT) dictates the ratio of ceramide to sphingomyelin within the cell. It is the only lipid transfer protein that specifically delivers ceramide from the endoplasmic reticulum to the Golgi apparatus, where ceramide serves as the substrate for sphingomyelin synthesis. In the past two decades, an increasing body of evidence has suggested a critical role of CERT in cancer, but much more intensive efforts are required to draw a definite conclusion. Herein, we review all research findings of CERT, focusing on its molecular structure, cellular functions and implications in cancer. This comprehensive review of CERT will help to better understand the molecular mechanism of cancer and inspire to identify novel druggable targets.

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Lack of glutathione peroxidase-8 in the ER impacts on lipid composition of HeLa cells microsomal membranes

Cited by 13 publications

References 39 publications

RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

RETRACTED ARTICLE: GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

The overexpression of GPX8 is correlated with poor prognosis in GBM patients

Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer

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