Ask about this productRelated genes to: Slc16a3 antibody
- Gene:
- SLC16A3 NIH gene
- Name:
- solute carrier family 16 member 3
- Previous symbol:
- -
- Synonyms:
- MCT3, MCT4
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-10
- Date modifiied:
- 2016-02-17
Related products to: Slc16a3 antibody
Related articles to: Slc16a3 antibody
- Extensive studies have implicated glycolytic reprogramming and lactate accumulation in immune evasion. However, clustered regularly interspaced short palindromic repeats (CRISPR)-based screens systematically interrogating metabolic drivers of immune checkpoint blockade resistance in clear cell renal cell carcinoma (ccRCC) remain scarce. Consequently, direct evidence delineating how the lactate exporter solute carrier family 16 member 3 (; monocarboxylate transporter 4, MCT4) rewires tumor lactate metabolism to promote immune escape in ccRCC is still lacking. - Source: PubMed
Publication date: 2026/04/24
Zuo ShidongDong JinkaiDong YuhaoFu ChengweiLi XuechaoZhao BaoboWang LuZhang YongjieKong LingshengYang TaoChen Lijun - Propionate, a gut microbiota-derived short-chain fatty acid, influences fetal development and postnatal metabolic programming. Although the fetus lacks microbiota and endogenous propionate production, human pregnancies show a fetal-to-maternal propionate concentration ratio greater than unity, suggesting concentrative transport across the placenta. However, its underlying mechanism remains undefined. The present study aimed to identify the transporter responsible for transplacental transport of propionate across the syncytiotrophoblast (SynT) layer. Transporter knockdown in human choriocarcinoma JEG-3 cells revealed that MCT1 (SLC16A1) silencing reduced [H]propionate uptake, whereas knockdown of other anion transporters had no effect. Functional assays using Xenopus oocytes demonstrated that the expression of human MCT1, but not MCT4 (SLC16A3), increased [H]propionate transport. In human trophoblast stem cell (hTSC)-derived SynT, [H]propionate uptake was pH-dependent and significantly inhibited by MCT1-selective inhibitors. Subsequently, to evaluate transcellular transport, we performed quantitative permeability assays using a hTSC-derived placental barrier model. [H]Propionate permeability was significantly higher than that of [C]d-mannitol, a paracellular marker. MCT1 inhibition reduced [H]propionate permeability in both apical-to-basal and opposite directions, whereas MCT4 inhibition had minimal effects. Notably, the hTSC-derived model exhibited a directional bias in [H]propionate transfer, reflecting the fetal-directed enrichment observed in vivo. Mathematical model analysis further indicated that MCT1 functions at both the apical and basal membranes to facilitate bidirectional transport of propionate. Together, these findings identify MCT1 as the predominant mediator of propionate transfer across the human SynT layer, providing mechanistic insights into how the placenta governs fetal exposure to maternal microbiota-derived metabolites. KEY POINTS: The fetus relies on maternal-derived propionate for development, but the molecular mechanism responsible for its concentrative transport across the human placenta remains undefined. Using multiple human trophoblast models and functional expression assays, we identified MCT1, but not MCT4, as the primary mediator of propionate transport. A human trophoblast stem cell-derived placental barrier model successfully exhibited a directional bias in propionate transfer, reflecting the fetal-directed enrichment observed in vivo. Mathematical modelling of the permeability data from the human trophoblast stem cell-derived barrier model indicates that MCT1 functions at both the apical and basal membranes of the syncytiotrophoblast to facilitate bidirectional transport. These findings establish MCT1 as a key gateway for transplacental propionate transfer, providing mechanistic insights into how the placenta regulates fetal exposure to maternal microbiota-derived metabolites. - Source: PubMed
Publication date: 2026/04/24
Tsuchitani ToshiakiMidorikawa RinKasuya AkariNoguchi SakiYamamoto KoheiNishimura TomohiroKaji HirokazuHori TakeshiTomi Masatoshi - Monocarboxylate transporter 4 (MCT4/SLC16A3) is frequently upregulated in human cancers and associated with aggressive progression and poor clinical outcomes. To elucidate its functional role, we establish MCT4 homozygous knockout BALB/c mice (MCT4) using CRISPR/Cas9-EGE technology. Compared with wild-type counterparts, MCT4 mice exhibit ~40% reduction in allograft tumor volume, which is partly attributable to diminished IGF1 production, as circulating and tumor interstitial IGF1 levels decrease by 40-45%. Exogenous IGF1 supplementation restores tumor growth, confirming this dependency. Moreover, MCT4 deficiency enhances antitumor immunity, characterized by increased infiltration of CD4⁺ and CD8⁺ T cells, NK cells, and macrophages, with a pronounced shift from immunosuppressive M2 to pro-inflammatory M1 macrophages. Consistently, across three independent carcinogenesis models (breast, lung, oral squamous cancers), MCT4 mice develop fewer and smaller lesions, underscoring its critical role in tumor incidence. Collectively, these findings identify MCT4 as a key driver of carcinogenesis through IGF1 regulation and immune modulation, highlighting its therapeutic potential. - Source: PubMed
Publication date: 2026/04/20
Wang ShuoGuo HailingFeng LujinWang XinyiZhang YujieLi XinZhou XiaojuMa Ningning - Triple-negative breast cancer (TNBC) exhibits hyperactive EGF (epidermal growth factor) signaling that drives metabolic plasticity and metastasis. Here, we identify secretory macroautophagy/autophagy as a key downstream effector linking EGF signaling to metabolic reprogramming that fuels TNBC metastatic progression. In TNBC cells, EGF stimulation redirected autophagosomes toward the plasma membrane through a SEC22B-dependent route, signifying activation of secretory autophagy. Proteomic profiling of purified autophagosomes revealed enrichment of the lactate transporter SLC16A3/MCT4 and its chaperone BSG/CD147 on autophagosomal membranes. Mechanistically, EGF promoted MAP1LC3/LC3-SLC16A3 interaction, facilitating SLC16A3 trafficking to the plasma membrane and enhancing lactate efflux. Genetic or pharmacological blockade of autophagy abrogated SLC16A3 surface localization, reduced extracellular lactate accumulation, and markedly suppressed lung metastasis originating from orthotopic TNBC tumors in mice. Although pharmacological inhibition of SLC16A3 effectively blocks its transporter activity and reduces lactate secretion, targeting autophagy provides a more precise approach to suppress EGF-driven SLC16A3 expression and the consequent rise in lactate secretion. Clinically, multiplex immunofluorescence of patient tumors demonstrated strong co-expression of EGFR, LC3, and SLC16A3, which correlated with poor disease-free survival. Our study reveals a previously unrecognized EGF-secretory autophagy axis that orchestrates metabolic remodeling in TNBC and highlights the therapeutic potential of targeting the secretory autophagy- SLC16A3-lactate pathway to restrain metastasis.: 3-MA: 3-methyladenine; ATG5: autophagy related 5; ATG7: autophagy related 7; APf: autophagosome fraction; CQ: chloroquine; CRISPR-Cas9: clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; ER: endoplasmic reticulum; ERBB2/HER2: erb-b2 receptor tyrosine kinase 2; GOBP: gene ontology biological process; imBI: induced metabolic bioluminescence imaging; i.p.: intraperitoneal injection; IVIS: in vivo imaging system; LAMP2: lysosomal associated membrane protein 2; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK/ERK: mitogen-activated protein kinase; PLA: proximity ligation assay; PNS: postnuclear supernatant; SEC22B: SEC22 homolog B, vesicle trafficking protein; shRNA: short hairpin RNA; SLC16A3/MCT4: solute carrier family 16 member 3; SNARE: soluble N-ethylmaleimide-sensitive-factor attachment protein receptor; TIRF: total internal reflection fluorescence; TME: tumor microenvironment; TNBC: triple-negative breast cancer; ULK1/Atg1: unc-51 like autophagy activating kinase 1. - Source: PubMed
Publication date: 2026/04/13
Wu Shan-YingLin Hung-JuLan Kai-YingChen Hong-ChenLin Chao-HsiungHsu Chih-YiLee Yi-JangChou Yen-YuChu Yeh-ShiuChiang Wei-ChungLiu Hsiao-ShengYeh Yuan-ChiehLan Sheng-Hui - Β-caryophyllene (BCP) is a plant compound that may exert bioactive effects on intestinal epithelial cell (IEC) function, including metabolism of butyrate, which is important for regulating cellular functions. The goal of this study was to investigate the effects of BCP on butyrate utilization in IEC. Caco-2 cells were grown on hanging, semi-permeable inserts as a model for the intestinal barrier. Treatments, including vehicle control, 40 µM BCP, 2 mM butyrate, and BUT plus BCP were added to the apical side of the insert and incubated for 24 and 48 h. Transepithelial electrical resistance (TEER; ohms/cm) was recorded to estimate barrier function and supernatant samples were taken from apical and basolateral sides. Butyrate and β-hydroxybutyrate (BHB) concentrations were measured by LC-MS to evaluate utilization of butyrate. Targeted gene expression analysis evaluated molecular modulation of BCP. Results suggested that the addition of BCP plus butyrate increased resistance compared to butyrate alone. The addition of BCP plus butyrate resulted in increased BHB production and greater butyrate disappearance. An upregulation of sodium-glucose transport 1 (SLC5A1), monocarboxylic transporters 1 and 4 (SLC16A1 and SLC16A3), and sodium hydrogen transporter 3 (SLC9A3) expression, and downregulation of 3-hydroxybutyrate dehydrogenase 1 (BDH1) and glucose transporter 2 (SLC2A2) expression were observed. These data indicate that BCP may promote the utilization of butyrate in intestinal epithelial cells and may influence barrier integrity. Overall, the results of this study support further investigation into the therapeutic potential of BCP. - Source: PubMed
Publication date: 2026/04/01
Scroggins HKent-Dennis CMay JHarmon D LKlotz J L