Ask about this productRelated genes to: SLC46A1 antibody
- Gene:
- SLC46A1 NIH gene
- Name:
- solute carrier family 46 member 1
- Previous symbol:
- -
- Synonyms:
- HCP1, MGC9564, PCFT
- Chromosome:
- 17q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2007-03-29
- Date modifiied:
- 2019-04-23
Related products to: SLC46A1 antibody
Related articles to: SLC46A1 antibody
- Source: PubMed
- The association between folate metabolism abnormalities and the development of colorectal cancer (CRC) remains controversial. Here, we report that the folate exerts a tumor-suppressive role in CRC; however, the manifestation of this effect is restricted by the expression level of folate transporter SLC46A1 in CRC cells. Multi-cohort profiling revealed significant downregulation of SLC46A1 in CRC tissues compared to adjacent normal tissues, where low expression independently predicted poor overall survival. Functional studies demonstrated that SLC46A1-mediated folate uptake suppressed tumor proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SLC46A1 deficiency restricted intracellular folate availability and impaired cellular methylation potential, as evidenced by a reduced SAM/SAH ratio, leading to DNA hypomethylation at specific sites such as the FOS proto-oncogene promoter. This epigenetic reprogramming triggers transcriptional activation of key oncogenic effectors CCND1, BCL2, and PLAU involved in CRC progression. Clinically, we found a significant inverse correlation between SLC46A1 expression and folate levels in tumor interstitial fluids of CRC, suggesting impaired folate uptake in low SLC46A1 tumors. Multi-color immunofluorescence across two cohorts further demonstrated conserved inverse associations between SLC46A1 and FOS expression in primary tumors and metastatic lesions. This study elucidates the molecular mechanism by which folate inhibits CRC progression through the "SLC46A1-epigenetic-transcriptional regulation" axis, providing mechanistic insights into folate deficiency-driven CRC progression and biomarkers for precision CRC intervention. This study elucidates the tumor-suppressive role of the folate transporter SLC46A1 in CRC. In normal cells, SLC46A1 facilitates folate uptake, supporting one-carbon metabolism and maintaining genomic stability. In CRC, however, SLC46A1 downregulation induces intracellular folate deficiency, triggering locus-specific DNA hypomethylation at the FOS promoter, which activates oncogenic transcription of key downstream effectors (CCND1, BCL2, PLAU), driving tumor progression. The graphical abstract illustrates the differential impact of SLC46A1 on folate metabolism and gene expression in normal versus tumor cells, highlighting its potential as a therapeutic target in CRC. - Source: PubMed
Publication date: 2026/01/31
Zhou YeluLiu YanxingLiu YiChe ChangZhao YihanYu JianingLi XinhangLi AngChen ShuyiWang HaojiaZhou MingzhenLiu DanHe WenfangWang ZhuoHan HuaWang XinLu YuanyuanWu KaichunZhao Xiaodi - Hereditary folate malabsorption is an autosomal recessive disorder caused by a pathogenic variant in SLC46A1, affecting proton-coupled folate transporter (PCFT) function. Infants with hereditary folate malabsorption often develop megaloblastic anemia and, without treatment, may experience serious neurodegenerative complications. Thalassemia is also an autosomal recessive genetic disorder. Major or compound heterozygous thalassemia is associated with severe complications and may require regular blood transfusions. - Source: PubMed
Publication date: 2025/12/05
Shekhawat Dolat SinghDidel SiyaramPurohit AbhishekSingh Kuldeep - Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by mutations in the SLC46A1 gene, leading to impaired intestinal and central nervous system folate transport. We present two male siblings with clinical features suggestive of HFM. The first infant exhibited pancytopenia, diarrhea, hypogammaglobulinemia, and neurological regression due to delayed diagnosis and treatment discontinuation, resulting in a fatal outcome. The second sibling was diagnosed early based on clinical suspicion and family history and showed favorable progress after timely parenteral folinic acid therapy. This report underscores the importance of early recognition, the limitations of genetic access in low-resource settings, and the critical role of parenteral folinic acid in preventing irreversible complications. - Source: PubMed
Publication date: 2025/08/11
N'joumi ChaimaeGhanam AyadTkak HassnaeBabakhouya AbdeladimRkain Maria - Antenatal steroid (ANS) therapy accelerates preterm lung maturation. Clinical and experimental data show current regimens disrupt placental function and transport and impact fetal growth. We have previously shown that higher materno-fetal steroid exposures increase fetal glucocorticoid clearance. Using a sheep model, we aimed to determine whether: (i) placental transcriptomic changes correlate with fetal glucocorticoid exposure; (ii) these changes persist below the threshold for lung maturation; and (iii) transcriptomic changes explain altered steroid clearance and fetal growth. - Source: PubMed
Publication date: 2025/09/02
Johnson Erin LUsuda HaruoCarter Sean W DIkeda HideyukiKumagai YusakuTakahashi TsukasaTakahashi YukiSaito YuyaWatson Hannah R SClarke Michael WIreland Demelza JNewnham John PSaito MasatoshiIllanes Sebastian ESesurajan Binny PriyaChoolani Mahesh AJobe Alan HKemp Matthew W