ArticleCancer cell2025
Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer.
Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- CPT1A-mediated IDO1 succinylation shapes EGFRvIII-driven resistance to tumor electric field therapy in glioblastoma.Nature communications · 2026Article
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Beyond the scaffold: extracellular matrix uptake in breast cancer.Biochemical Society transactions · 2026Review
- Exploiting Macropinocytosis Drives Redox Vulnerability to Preferentially Target Drug-Resistant Cancer.ACS nano · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Single-cell RNA sequencing in ovarian cancer: decoding the tumor microenvironment for personalized therapy.Journal of ovarian research · 2026Review
- Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)PCell death & disease · 2026Article
- Microplastics as Vectors Influencing Oxidative Stress, Inflammation, and Endocrine Function During Early Development.International journal of molecular sciences · 2026Review
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study.PLoS medicine · 2026Article
- An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Spatially defined danger zone shapes gastric cancer progression through CCDC80Apoptosis : an international journal on programmed cell death · 2026Article
- Decoding the Integrated Stress Response of Pancreatic Cancer: Identifying a Serine-dependent Tumor Subset Under Metabolic Relationships With CAFs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
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18 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) tumors are glutamine deficient, and both tumor cells and cancer-associated fibroblasts (CAFs) rely on this amino acid to maintain fitness and induce macropinocytosis as an adaptive response. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive. In this study, we find that macropinocytosis sustains the myCAF phenotype under glutamine limitation by preventing inflammatory reprogramming. Our data demonstrate that metabolic stress induces an intrinsic inflammatory CAF (iCAF) program through MEK-ERK signaling. We find that blocking macropinocytosis in vivo promotes myCAF-to-iCAF transitions, remodeling the tumor stroma. Importantly, stromal remodeling driven by macropinocytosis inhibition-including iCAF enrichment, collagen reduction, immune cell infiltration, and vascular expansion-sensitizes PDAC tumors to immunotherapy and chemotherapy. Our findings reveal that inhibiting macropinocytosis promotes an inflammatory, less fibrotic tumor microenvironment that can be leveraged to improve therapeutic responses in PDAC.
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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.