ArticleBritish journal of cancer2021
SLC38A4 functions as a tumour suppressor in hepatocellular carcinoma through modulating Wnt/β-catenin/MYC/HMGCS2 axis.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 97 citations in OpenAlex.
- SLC38A4 promotes Kupffer cell phagocytosis and suppresses tumor liver metastasis.Experimental & molecular medicine · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Amino Acid Transporters in Glioblastoma: Implications for Diagnosis, Disease Monitoring, Therapeutic Targeting, and Drug Delivery.Molecular diagnosis & therapy · 2025Review
- SLC38A4 as a prognostic biomarker and correlated with immune infiltration in colorectal liver metastasis.Discover oncology · 2025Article
- mCancer cell international · 2025Article
- JAK2/STAT3/HMGCS2 signaling aggravates mitochondrial dysfunction and oxidative stress in hyperuricemia-induced cardiac dysfunction.Molecular medicine (Cambridge, Mass.) · 2025Article
- mCellular and molecular life sciences : CMLS · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Molecular characterization of ovarian mesonephric-like adenocarcinoma: Insights from single-cell RNA sequencing and mitochondrial metabolism.Gynecologic oncology reports · 2025Article
- Role of the Wnt/β-catenin signaling pathway in the development of HCC.Frontiers in immunology · 2025Review
- Article
- Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.Clinical and translational medicine · 2024Article
- Peptidomic analysis reveals novel peptide PDLC promotes cell proliferation in hepatocellular carcinoma via Ras/Raf/MEK/ERK pathway.Scientific reports · 2024Article
- Determining expression changes of ANO7 and SLC38A4 membrane transporters in colorectal cancer.Heliyon · 2024Article
- Covalent Degrader of the Oncogenic Transcription Factor β-Catenin.Journal of the American Chemical Society · 2024Article
- Induction of resistance to neurotrophic tropomyosin-receptor kinase inhibitors by HMGCS2 via a mevalonate pathway.Cancer medicine · 2024Article
- METTL3 and METTL14-mediated NScientific reports · 2024Article
- Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11.Antioxidants (Basel, Switzerland) · 2024Article
- DNMT3L inhibits hepatocellular carcinoma progression through DNA methylation of CDO1: insights from big data to basic research.Journal of translational medicine · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and therapeutic target for HCC.
methodsExpression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets.
resultsSLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/β-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC.
conclusionsSLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.
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