Ask about this productRelated genes to: SLC38A3 antibody
- Gene:
- SLC38A3 NIH gene
- Name:
- solute carrier family 38 member 3
- Previous symbol:
- -
- Synonyms:
- G17, SN1
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-22
- Date modifiied:
- 2016-10-05
Related products to: SLC38A3 antibody
Related articles to: SLC38A3 antibody
- Biallelic mutations in SLC38A3 lead to postnatal progressive microcephaly, epilepsy, and intellectual disability. However, the underlying pathophysiology remains unknown. Here, we identified Slc38a3 expressed at the vascular endothelium as a critical glutamine transporter that mediates blood-to-brain influx of glutamine through the blood-brain barrier (BBB). Endothelial selective deletion of Slc38a3 (Slc38a3-cKO) lowered the influx of glutamine across the BBB and decreased brain glutamine levels in mouse pups. This was associated with lower transfer of glutamine carbons to glutamate and GABA, suggesting impairment of the glutamine-glutamate/GABA metabolic cycle. Like individuals with mutations in SLC38A3, Slc38a3-cKO pups developed postnatal progressive microcephaly as well as behavioural impairments and morphological alterations in synapses. Approximately 30% of Slc38a3-cKO pups fail to thrive, exhibiting motor dysfunction and preweaning lethality. Glutamine deficiency in the Slc38a3-cKO hippocampus was associated with a slower TCA cycle and a seemingly adaptive increase in glycolysis rate. Glutamine supplementation replenished brain glutamine, prevented microcephaly, and normalized motor behavior in Slc38a3-cKO pups, indicating that brain glutamine deficiency is the primary cause of the phenotype. In contrast to the dogma that all glutamine is produced locally in the brain, our data show that Slc38a3 provides blood-derived glutamine for neurotransmitter synthesis, energy metabolism, and synaptogenesis. Our findings suggest that SLC38A3 mutations cause a glutamine-related BBB aminoacidopathy and developmental disorder, which may be amenable to glutamine supplementation therapy. - Source: PubMed
Publication date: 2025/12/24
Radzishevsky InnaHarb LamaOdeh MaaliMaoz InonSaeed AseelLahkar AnkitaAgranovich BellaAbramovich IfatChaudhry Farrukh AAvital AviLiebl Daniel JWolosker Herman - Bone cancer pain (BCP), one of the most intractable symptoms in patients with cancer, remains poorly understood and lacks effective therapeutic interventions. In this study, we employed an established rat model of BCP induced by intratibial injection of MRMT-1 mammary carcinoma cells. Transcriptomic profiling of the L4-L6 dorsal root ganglia (DRGs) revealed an upregulation of the amino acid transporter SLC38A3. This finding was further confirmed by time-dependent increases in both its mRNA and protein levels. Immunofluorescence co-localization indicated that SLC38A3 was expressed in NF200-, CGRP-, and IB4-positive neurons within the L4-L6 DRGs, and its expression was upregulated in the BCP model. Concomitantly, the transient receptor potential vanilloid 1 (TRPV1) expression in BCP rat DRGs was dynamically upregulated at both the mRNA and protein levels, aligning temporally with pain hypersensitivity. Lentivirus-mediated overexpression or knockdown of SLC38A3 in the DRGs led to a corresponding upregulation or downregulation of TRPV1-expression. Activation of the PI3K/AKT signaling pathway corresponds with BCP-related pain behaviors and expression patterns of SLC38A3 and TRPV1. Bexarotene alleviates BCP in rats by suppressing the aberrant overexpression of SLC38A3, thereby blocking the PI3K/AKT signaling pathway-mediated upregulation of TRPV1. These findings indicate that SLC38A3, through its downstream PI3K/AKT-TRPV1 axis, may serve as a potential molecular mechanism for analgesia in BCP. - Source: PubMed
Publication date: 2025/10/29
Cheng Yu-NaZhang Ming-ZhuXie Cui-QingLi Zhi-QiGe You-FengJin Zhao-HuiLuo Zhi-HuaZheng Chen-YangChen LiangFang DongNiu Chen-GuangHe Jin-Jin - Hepatocellular carcinoma (HCC) is the third most common cause of death for cancer patients globally, with an overall 5-year survival rate of only 16%. The molecular mechanisms leading to malignant progression of HCC patients remain largely unclear. Hepatocyte nuclear factor 4α (HNF4α) functions as a tumor-suppressive transcription factor (TF) in HCC. In this study, we aimed to identify functional HCC susceptibility single nucleotide polymorphisms (SNPs) in HNF4α-binding sites throughout the human genome. We identified 1274 HNF4α-binding site polymorphisms via a genome-wide screening using TUIFGA (the updated integrative functional genomics approach), which we previously developed to recognize cancer susceptibility SNPs within genome-wide TF-binding sites. Among these SNPs, the DEAF1 rs11246280 SNP was significantly associated with HBV-related HCC susceptibility in several case-control studies. Importantly, the rs11246280 SNP could interrupt HNF4α binding to the DEAF1 promoter and enhance DEAF1 expression. Oncogenic TF DEAF1 binds to the SLC38A3 promoter, elevates glutamine transporter SLC38A3 expression, enhances influx of glutamine and GSH production, leads to reduced ROS levels in cells and, thereby, promotes HCC progression. Our findings highlighted the role of DEAF1 during HCC development via maintaining redox balance, which sheds light on the development of novel cancer therapeutics. - Source: PubMed
Huang LinyingYu XinyuanZhang ZiqiHuo YanfeiZhang LongZhang NashaYang Ming - The sodium/calcium exchanger (NCX) type 1 has been well described in various cancers, but little is known about the other two NCX types (NCX2 and NCX3). In this study, we used the selective blocker of NCX3 - YM-244769 to investigate changes in apoptosis induction, migration, proliferation, intracellular calcium and ATP in four cancer cell lines - DLD1, HeLa, MDA-MB-231 and JIMT1. In all four cell lines we observed a concentration-dependent increase in the number of apoptotic cells, as well as reduced migration and proliferation. Induction of hypoxic conditions did not alter the response of these cells to YM-244769 in any of the above-mentioned parameters. These results indicate the role of NCX3 in cancer cell migration, proliferation and apoptosis, as inhibition of NCX1 by the specific blocker SEA0400 had no significant effect on these parameters. However, we verified the effect of NCX3 inhibition by using CRISPR/Cas9 to generate clones in which the SLC8A3 (NCX3) gene was deleted, and we obtained the same results. In addition, mitochondrial respiration was impaired in the clones with NCX3 knocked-out, suggesting that NCX3 also play a role in bioenergetics. In conclusion, we have clearly shown that NCX3 plays an important anti-apoptotic, pro-migratory and proliferative role in the cancer cells by affecting mitochondrial bioenergetics, thus supporting their survival and fate. - Source: PubMed
Publication date: 2025/04/30
Galvankova KristinaRezuchova IngeborgKlena LadislavGrman MarianGazova SimovaLiskova VeronikaKozovska ZuzanaRoller LadislavBabula PetrKrizanova Olga - Metabolic syndrome associated with glucose metabolism plays a pivotal role in tumorigenesis, potentially elevating the risk of endometrial cancer (EC). This study sought to establish a glucose metabolism-related gene (GMRG) signature linked to EC. - Source: PubMed
Publication date: 2025/01/07
Jiang JuanXia NanYang MeiQiu PingZhu WeiChen JingZhu Jiamei