SLC1A5

Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs...

Osteoarthritis (OA) is a chronic joint disease that reduces quality of life for patients. Ferroptosis plays a significant role in OA. However, its underlying mechanism remains unclear. In this study, we integrated 7 OA synovial datasets from the GEO database to screen for significant ferroptosis-related genes. The top 5 ferroptosis regulators were used to construct nomogram models to predict OA prevalence. Consensus clustering was applied to classify OA patients into different ferroptosis patterns based on significant ferroptosis-related genes...

Diabetic kidney disease (DKD) is a leading diabetic complication causing significant mortality among people around the globe. People with poor glycemic control accompanied by hyperinsulinemia, dyslipidemia, hypertension, and obesity develop diabetic complications. These diabetic patients develop epigenetic changes and suffer from diabetic kidney complications even after subsequent glucose control, the phenomenon that is recognized as metabolic memory. DNA methylation is an essential epigenetic modification that contributes to the development and progression of several diabetic complications, including DKD...

Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not...

Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44...

Proteostasis requires oxidative metabolism (ATP) and mitigation of the associated damage by glutathione, in an increasing dysfunctional relationship with aging. SLC3A2 (4F2hc, CD98) plays a role as a disulfide-linked adaptor to the SLC7A5 and SLC7A11 exchangers which import essential amino acids and cystine while exporting Gln and Glu, respectively. The positions of N-glycosylation sites on SLC3A2 have evolved with the emergence of primates, presumably in synchrony with metabolism. Herein, we report that each of the four sites in SLC3A2 have distinct profiles of Golgi-modified N-glycans...

The non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serine de novo , others are auxotrophic for serine and therefore reliant on the uptake of exogenous serine. Importantly, however, the transporter(s) that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (coded for by the gene SLC1A5 ) as the primary serine transporter in cancer cells. ASCT2 is well-known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2...

BACKGROUND: Targeting glycolysis in cancer is an attractive approach for therapeutic intervention. 2-Deoxyglucose (2DG) is a synthetic glucose analog that inhibits glycolysis. However, its efficacy is limited by the systemic toxicity at high doses. Understanding the mechanism of 2DG resistance is important for further use of this drug in cancer treatment. METHODS: The expression of thioredoxin-1 (Trx-1) in colorectal cancer (CRC) cells treated with 2DG was detected by Western blotting...

BACKGROUND: B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts...

INTRODUCTION: The tumor microenvironment of hepatocellular carcinoma is composed of multiple cells, and the interactive communication between cells drives tumor progression and characterizes the tumor. Communication between cells is mainly achieved through signal transduction between receptor ligands, and the rise of single-cell technology has made it possible to analyze the communication network between cells. METHODS: We applied a train of bioinformatic techniques and in vitro experiments...

High levels of YAP1 and ferroptosis activation in castration-resistant prostate cancer (CRPC) can inhibit CRPC progression and improve its sensitivity toward chemotherapeutics drugs. However, whether YAP1 regulates ferroptosis in CRPC cells and the underlying mechanisms are unknown. The protein levels of YAP1, SLC1A5, and GLS1 in benign prostatic hyperplasia (BPH), prostate cancer (PCa) that did not progress to CRPC, and CRPC tissue samples were evaluated using western blotting. In PC-3 and DU-145 cells, YAP1 overexpression vector, small-interfering RNA, specific inhibitor verteporfin, ferroptosis-inducer RSL3, SLC1A5-inhibitor V-9302, and GLS1-inhibitor CB-839 were used...

This study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect ( p > 0...

Lung cancer is a major health concern and significant barrier to human well-being and social development. Although targeted therapy has shown remarkable progress in the treatment of lung cancer, the emergence of drug resistance has limited its clinical efficacy. Sijunzi Tang (SJZ) is a classical Chinese herbal formula known for tonifying qi and nourishing the lungs, has been recognized for its potential in lung cancer management. However, the underlying mechanism of its combined use with anti-cancer drugs remains unclear...

OBJECTIVE: Solid tumor cells utilize amino acid transporters (AATs) to increase amino acid uptake in response to nutrient-insufficiency. The upregulation of AATs is therefore critical for tumor development and progression. This study identifies the upregulated AATs under amino acid deprived conditions, and further determines the clinicopathological importance of these AATs in evaluating the prognosis of patients with cancers. MATERIALS AND METHODS: In this experimental study, the Gene Expression Omnibus (GEO) datasets (GSE62673, GSE26370, GSE125782 and GSE150874) were downloaded from the NCBI website and utilized for integrated differential expression and pathway analysis v0...

Ferroptosis results from metabolic dysregulation and is closely linked to liver cancer. Although a ferroptosis-related gene signature in liver cancer has been established, the precise regulatory mechanism is still unclear. To identify shared pathogenic genes linked to ferroptosis across liver cancer patients from diverse racial backgrounds, we evaluated various ferroptosis-related genes, constructing a signature for both Asian and White patients using The Cancer Genome Atlas (TCGA) database. Based on the differential expression and functionality of ferroptosis-associated genes, we selected Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Acyl-CoA synthetase long-chain 4 (ACSL4) and Endoplasmic reticulum membrane protein complex 2 (EMC2) for further study in liver cancer cells...

The prognosis of low-grade glioma (LGG) is highly variable and requires more accurate predictors. Ferroptosis, a newly discovered programmed cell death, has been demonstrated to play a crucial role in some types of tumors. However, prognostic prediction based on ferroptosis-related genes (FRGs) and the influence on the tumor microenvironment (TME) in LGG remains elusive. We derived expression profiles for LGG from public databases. Based on the expression of 25 FRGs in LGG, two independent subtypes and a risk model were successfully constructed...

Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues...

System-level analysis of single-cell data is rapidly transforming the field of immunometabolism. Given the competitive demand for nutrients in immune microenvironments, there is a need to understand how and when immune cells access these nutrients. Here, we describe a new approach for single-cell analysis of nutrient uptake where we use in-cell biorthogonal labeling of a functionalized amino acid after transport into the cell. In this manner, the bona fide active uptake of glutamine via SLC1A5/ASCT2 could be quantified...

BACKGROUND: Hepatitis B virus (HBV)-infected population accounts for approximately 50% of all hepatocellular carcinoma (HCC) cases and has a relatively poor prognosis. Although the significant role of ferroptosis in the development and therapeutic response of various cancers has been validated, the key ferroptosis-related genes (FRGs) on the stratification of HBV-associated HCC are still unclear. METHODS: Through the random forest, GSVA and Cox regression analyses, we established a comprehensive prognostic system covering multiple FRGs to elevate the predictive accuracy for the survival rate of HBV-related HCC using information obtained from public databases...

The neutral amino acid glutamine plays a central role in TGF-β (transforming growth factor-β)-induced myofibroblast activation and differentiation. Cells take up glutamine mainly through a transporter expressed on the cell surface known as solute carrier SLC1A5 (solute carrier transporter 1A5). In the present work, we demonstrated that profibrotic actions of TGF-β are mediated, at least in part, through a metabolic maladaptation of SLC1A5 and that targeting SLC1A5 abrogates multiple facets of fibroblast activation...