ArticleNature2016
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 737 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
737 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,078 citations in OpenAlex.
- The dual role of autophagy in HPV-positive head and neck squamous cell carcinoma: a systematic review.Journal of cancer research and clinical oncology · 2024Pooled it
- Research progress of pancreatic cancer based on ferroptosis-cuproptosis interaction (Review).Oncology letters · 2026Review
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Cancer metastasis: biological mechanisms, therapeutic bottlenecks, and emerging interventions.Journal of hematology & oncology · 2026Review
- Transcriptomic profiling reveals autophagy-associated programs and prognostic biomarkers in anoikis-resistant pancreatic cancer cells.BMC cancer · 2026Article
- ALKBH5 in Cancer-Associated Fibroblasts Governs an Epitranscriptomic Axis That Drives Pancreatic Cancer Metastasis.Cancer research · 2026Article
- Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review).Oncology letters · 2026Review
- Review
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Article
- Epigenomic Remodeling by Lipid Metabolism: A Cross-Disease Perspective on Cancer and Brain Disorders.Genes · 2026Review
- Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and Curative-Intent Resection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Desmoplasia and therapeutic resistance in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- Blocking L-carnitine synthesis by meldonium prolongs the survival in mice with pancreatic cancer.iScience · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Integrated multi-omics and single-cell analyses identify metabolic heterogeneity and therapeutic vulnerabilities in medullary thyroid cancer.British journal of cancer · 2026Article
677 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.
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What OpenQuestion holds
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.