Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer

Zhao, Yangjing; Wang, Hui; Zhou, Jing‐Dong; Shao, Qixiang

doi:10.3390/cancers14102560

Cited by 42 publications

(36 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antioxidant GPX1 was reported that it played a vital role in normal cell growth and adaptive pathological reaction, such as apoptosis or inflammation 67 . However, the aberrantly increased expression levels of GPX1 in many cancers were closely related to tumorigenesis and progression 55 . Previous researches had already revealed that the abnormally increased GPX1 activity could decrease tumor sensitivity toward ROS‐generating anticancer drugs 68,69 .…”

Section: Discussionmentioning

confidence: 99%

Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer

Zhu,

Pu,

Zhang

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

BackgroundSelenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium‐containing protein as a mediator. Of note, the previous studies reported that the expression of selenium‐binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non‐small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear.MethodsThe expression of SELENBP1 was measured by qRT‐PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK‐8, colony formation, wound‐haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay.ResultsWe further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT‐II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase‐3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress.ConclusionsOur findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer

Zhu,

Pu,

Zhang

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…Among them, the expression levels of six genes (PECR, OLAH, ACOT11, ACAT2, NUDT19, PTGIS) were significantly upregulated and 4 genes (GPX1, ADH5, PTGR1, ACADS) were downregulated in UCEC samples compared to normal tissues, which have been validated by PCR experiment. Substantial evidence revealed that most of these FAMGs functioned as oncogenes or tumorsuppressor genes in various cancers (29)(30)(31)(32)(33)(34)(35)(36). We also determined the prevalence of genetic mutation in UCEC samples, as well as CNV alterations.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis and experimental validation reveals fatty acid metabolism-related prognostic signature and immune responses for uterine corpus endometrial carcinoma

Guo

He²,

Chen³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundUterine corpus endometrial carcinoma (UCEC) is the third most common gynecologic malignancy. Fatty acid metabolism (FAM) is an essential metabolic process in the immune microenvironment that occurs reprogramming in the presence of tumor signaling and nutrient competition. This study aimed to identify the fatty acid metabolism-related genes (FAMGs) to develop a risk signature for predicting UCEC.MethodsThe differentially expressed FAMGs between UCEC samples and controls from TCGA database were discovered. A prognostic signature was then constructed by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses. Based on the median risk score, UCEC samples were categorized into high- and low-FAMGs groups. Kaplan-Meier (K-M) curve was applied to determine patients’ overall survival (OS). The independent prognostic value was assessed by uni- and multivariate analyses. The associations between the risk score and immune status, immune score, and drug resistance were evaluated. Quantitative Real-time PCR (qRT-PCR) was utilized to confirm FAMGs expression levels in UCEC cells.ResultsWe built a 10-FAMGs prognostic signature and examined the gene mutation and copy number variations (CNV). Patients with a high-FAMGs had a worse prognosis compared to low-FAMGs patients in TCGA train and test sets. We demonstrated that FAMGs-based risk signature was a significant independent prognostic predictor of UCEC. A nomogram was also created incorporating this risk model and clinicopathological features, with high prognostic performance for UCEC. The immune status of each group was varied, and immune score was higher in a low-FAMGs group. HLA-related genes such as DRB1, DMA, DMB, and DQB2 had higher expression levels in the low-FAMGs group. Meanwhile, high-FAMGs patients were likely to response more strongly to the targeted drugs Bortezomib, Foretinib and Gefitinib. The qRT-PCR evidence further verified the significant expression of FAMGs in this signature.ConclusionsA FAMGs-based risk signature might be considered as an independent prognostic indicator to predict UCEC prognosis, evaluate immune status and provide a new direction for therapeutic strategies.

show abstract

“…As GPXs detoxify ROS, it is therefore unsurprising that they are involved in detoxifying ROS generated by cancer cells. GPX1, a Se-sensitive selenoprotein whose complex roles in cancer have already been reviewed in detail [ 91 ], was reported to be involved in protective autophagy in pancreatic ductal adenocarcinoma (PDA) cells during glucose deprivation. GPX1 overexpression sensitized PDA cells to caspase-dependent apoptosis [ 86 ].…”

Section: Impact Of Selenoproteins On Cancermentioning

confidence: 99%

Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers

et al. 2022

View full text Add to dashboard Cite

A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se is metabolized and incorporated as the amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs), among others. Both the processes of Se and Sec metabolism for the production of selenoproteins and the action of selenoproteins are utilized by cancer cells from solid tumors as a protective mechanism against oxidative damage and to resist ferroptosis, an iron-dependent cell death mechanism. Protection against ferroptosis in cancer cells requires sustained production of the selenoprotein GPX4, which involves increasing the uptake of Se, potentially activating Se metabolic pathways such as the trans-selenation pathway and the TXNRD1-dependent decomposition of inorganic selenocompounds to sustain GPX4 synthesis. Additionally, endoplasmic reticulum-resident selenoproteins also affect apoptotic responses in the presence of selenocompounds. Selenoproteins may also help cancer cells adapting against increased oxidative damage and the challenges of a modified nutrient metabolism that result from the Warburg switch. Finally, cancer cells may also rewire the selenoprotein hierarchy and use Se-related machinery to prioritize selenoproteins that are essential to the adaptations against ferroptosis and oxidative damage. In this review, we discuss both the evidence and the gaps in knowledge on how cancer cells from solid tumors use Se, Sec, selenoproteins, and the Se-related machinery to promote their survival particularly via resistance to ferroptosis.

show abstract

Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer

Cited by 42 publications

References 91 publications

Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer

Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer

Integrated bioinformatics analysis and experimental validation reveals fatty acid metabolism-related prognostic signature and immune responses for uterine corpus endometrial carcinoma

Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers

Contact Info

Product

Resources

About