ArticleCancer discovery2020
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer.
Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
122 citing papers in PubMed, 170 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
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- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- A Urinary Three-Metabolite Signature Enables Noninvasive Identification of Patients with High-Risk Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Glycolytic cancer-associated fibroblasts orchestrate metabolic remodeling in the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Metabolic Salvage and Acyl-chain Remodeling Support Glycosphingolipid Synthesis within the PDAC Tumor Microenvironment.bioRxiv : the preprint server for biology · 2026Article
- Cancer-associated fibroblasts regulate DNA repair in pancreatic cancer through NDRG1-mediated R-loop processing.Nature cell biology · 2026Article
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- The Significance of the Heterogeneity of Cancer-Associated Fibroblasts in Tumor Microenvironments.Metabolites · 2026Review
- Vertical RAS pathway inhibition in pancreatic cancer drives therapeutically exploitable mitochondrial alterations.Signal transduction and targeted therapy · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Analysis of metabolic rewiring in MDR1-overexpressing drug-resistant glioblastoma.Frontiers in pharmacology · 2026Article
- Cancer-associated fibroblasts: central players in cancer hallmarks and therapeutic resistance.Cell communication and signaling : CCS · 2025Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Expression of IMPACT Curtails Metabolic Plasticity and Augments NK Cell Killing to Abrogate Metastatic Growth.Cancer discovery · 2025Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) evolves a complex microenvironment comprised of multiple cell types, including pancreatic stellate cells (PSC). Previous studies have demonstrated that stromal supply of alanine, lipids, and nucleotides supports the metabolism, growth, and therapeutic resistance of PDAC. Here we demonstrate that alanine cross-talk between PSCs and PDAC is orchestrated by the utilization of specific transporters. PSCs utilize SLC1A4 and other transporters to rapidly exchange and maintain environmental alanine concentrations. Moreover, PDAC cells upregulate SLC38A2 to supply their increased alanine demand. Cells lacking SLC38A2 fail to concentrate intracellular alanine and undergo a profound metabolic crisis resulting in markedly impaired tumor growth. Our results demonstrate that stromal-cancer metabolic niches can form through differential transporter expression, creating unique therapeutic opportunities to target metabolic demands of cancer. SIGNIFICANCE: This work identifies critical neutral amino acid transporters involved in channeling alanine between pancreatic stellate and PDAC cells. Targeting PDAC-specific alanine uptake results in a metabolic crisis impairing metabolism, proliferation, and tumor growth. PDAC cells specifically activate and require SLC38A2 to fuel their alanine demands that may be exploited therapeutically.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.