ArticleScientific reports2019
CD98hc (SLC3A2) sustains amino acid and nucleotide availability for cell cycle progression.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Urinary metabolomic profiling to identify the impact of the increased intake of whole grains, vegetables, and fruits in healthy adolescents.European journal of clinical nutrition · 2026Article
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- Regulation of Amino Acid Transporters by Cell Surface Receptors.Antioxidants (Basel, Switzerland) · 2026Review
- BCAT1 inhibits glutamine-dependent Akt/mTOR signaling and nucleotide synthesis by initiating BTRC-mediated degradation of SLC3A2 in pancreatic adenocarcinoma.Cancer & metabolism · 2026Article
- LAT1/SLC7A5-mediated amino acid uptake is regulated by redox signals triggered by formyl-peptide receptor 2.The FEBS journal · 2026Article
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- Epigenetically-Upregulated CD98 Shed Light on the Precancerous Diagnosis and Prognosis Prediction of Esophageal Cancer.Cancer science · 2025Article
- Integrated in vivo functional screens and multiomics analyses identify α-2,3-sialylation as essential for melanoma maintenance.Science advances · 2025Article
- Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI.Metabolites · 2025Review
- RTN4IP1 Contributes to ESCC via Regulation of Amino Acid Transporters.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CD98hc, a novel of galectin-8 receptor, binds to galectin-8 in an N-glycosylation-dependent manner.Acta biochimica et biophysica Sinica · 2025Article
- NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis.Nature metabolism · 2025Article
- Disulfidptosis-related gene SLC3A2: a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma.Frontiers in oncology · 2025Article
- Coordination between the eIF2 kinase GCN2 and p53 signaling supports purine metabolism and the progression of prostate cancer.Science signaling · 2024Article
- A monoclonal antibody recognizing CD98 on human embryonic stem cells shows anti-tumor activity in hepatocellular carcinoma xenografts.Cancer immunology, immunotherapy : CII · 2024Article
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
- Amino acid metabolism in tumor biology and therapy.Cell death & disease · 2024Review
- Hsa_circ_0050900 affects ferroptosis in intrahepatic cholangiocarcinoma cells by targeting hsa‑miR-605‑3p to regulate SLC3A2.Oncology letters · 2024Article
- Review
- CD98 heavy chain as a prognostic biomarker and target for cancer treatment.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.
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