ArticleiScience2025
Tumor microenvironment acidosis favors pancreatic cancer stem cell properties and
Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- TRPV6-Mediated CaCancers · 2026Review
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications.Cancer cell · 2026Review
- The Acidic Exosomal miR-1246/WASF3 Axis Regulates Hepatic Stellate Cell Activation and Stiff ECM Remodeling to Promote Pancreatic Ductal Adenocarcinoma Liver Metastasis.International journal of biological sciences · 2026Article
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Acidic melanoma microenvironment selects for a senescence-like but also migratory-active subpopulation driving metastatic disease.Cell death discovery · 2025Article
- Review
- Reprogramming the immune microenvironment in lung cancer.Frontiers in immunology · 2025Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The acidic tumor microenvironment (TME) favors cancer aggressiveness via incompletely understood pathways. Here, we asked whether adaptation to environmental acidosis (pH 6.5) selects for human pancreatic cancer stem cell (CSC) properties. RNA sequencing (RNA-seq) of acid-adapted (AA) Panc-1 cells revealed CSC pathway enrichment and upregulation of CSC markers. AA Panc-1 cells exhibited classical CSC characteristics including increased aldehyde dehydrogenase (ALDH) activity and β-catenin activity. Panc-1, PaTu8988s, and MiaPaCa-2 cells all exhibited increased pancreatosphere-forming efficiency after acid adaptation but differed in CSC marker expression and did not exhibit typical flow cytometric CSC populations. However, single-nucleus sequencing revealed the acid adaptation-induced emergence of Panc-1 cell subpopulations with clear CSC characteristics. In orthotopic mouse tumors, AA Panc-1 cells exhibited enhanced aggressiveness, liver and lung metastasis, compared to controls. Collectively, our work suggests that acid adaptation enriches for pancreatic CSC phenotypes with unusual traits via several trajectories, providing new insight into how acidic microenvironments favor cancer aggressiveness.
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