SynthesisClinical cancer research : an official journal of the American Association for Cancer Research2021
PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions.
Synthesis in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Heterogeneity of glucose metabolism and uptake identifies distinct cancer cell and cancer stem cell phenotypes.Cellular & molecular biology letters · 2026Article
- Mitochondrial metabolism in cancer stem cells (CSCs): molecular and diagnostic implications.Frontiers in molecular biosciences · 2026Review
- Metabolic and immune crosstalk between cancer-associated fibroblasts and pancreatic cancer cells.Journal of translational medicine · 2025Review
- DNMBP-AS1/hsa-miR-30a-5p/PGC1α axis suppresses tumor progression of colorectal cancer by inhibiting PKM2-mediated Warburg effect and enhance anti-PD-1 therapy efficacy.Cell death discovery · 2025Article
- Dual Role of NRF2 in Pancreatic Precursor Lesions.Cancer research communications · 2025Article
- Transplantation of gastric epithelial mitochondria into human gastric cancer cells inhibits tumor growth and enhances chemosensitivity by reducing cancer stemness and modulating gastric cancer metabolism.Stem cell research & therapy · 2025Article
- Lactylation in tumor: mechanisms and therapeutic potentials.Frontiers in immunology · 2025Review
- Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.International journal of molecular sciences · 2024Article
- Article
- Cancer-Associated Fibroblast Induces Acinar-to-Ductal Cell Transdifferentiation and Pancreatic Cancer Initiation Via LAMA5/ITGA4 Axis.Gastroenterology · 2024Article
- The CPT1A/Snail axis promotes pancreatic adenocarcinoma progression and metastasis by activating the glycolytic pathway.iScience · 2023Article
- Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.Journal of translational medicine · 2023Review
- Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.Theranostics · 2023Article
- Tumor microenvironment interactions with cancer stem cells in pancreatic ductal adenocarcinoma.Advances in cancer research · 2023Review
- PAF1 cooperates with YAP1 in metaplastic ducts to promote pancreatic cancer.Cell death & disease · 2022Article
- Mitochondrial Fission and Fusion in Tumor Progression to Metastasis.Frontiers in cell and developmental biology · 2022Review
- Ubiquilin 1 suppresses the cancer stem cell-like traits of non-small cell lung cancer cells by regulating reactive oxygen species homeostasis.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMetabolic reprogramming and cancer stem cells drive the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). However, the metabolic and stemness programs of pancreatic precursor lesions (PPL), considered early PDAC development events, have not been thoroughly explored. EXPERIMENTAL
designMeta-analyses using gene expression profile data from NCBI Gene Expression Omnibus and IHC on tissue microarrays (TMA) were performed. The following animal and cellular models were used: cerulean-induced KrasG12D; Pdx1 Cre (KC) acinar-to-ductal metaplasia (ADM) mice, KrasG12D; Smad4Loss; Pdx-1 Cre (KCSmad4-) intraductal papillary mucinous neoplasm (IPMN) mice, LGKC1 cell line derived from the doxycycline-inducible Gnas IPMN model, and human IPMN organoids. Flow cytometry, Seahorse extracellular flux analyzer, qRT-PCR, and sphere assay were used to analyze metabolic and stemness features. SR18292 was used to inhibit PGC1α, and short hairpin RNA was used to knockdown (KD) PGC1α.
resultsThe meta-analysis revealed a significant upregulation of specific stemness genes in ADM-mediated pancreatic intraepithelial neoplasms (PanIN) and IPMN. Meta- and TMA analyses followed by in vitro and in vivo validation revealed that ADM/PanIN exhibit increased PGC1α and oxidative phosphorylation (OXPhos) but reduced CPT1A. IPMN showed elevated PGC1α, fatty acid β-oxidation (FAO) gene expression, and FAO-OXPhos. PGC1α was co-overexpressed with its coactivator NRF1 in ADM/PanINs and with PPARγ in IPMN. PGC1α KD or SR18292 inhibited the specific metabolic and stemness features of PPLs and repressed IPMN organoid growth.
conclusionsADM/PanINs and IPMNs show specific stemness signatures with unique metabolisms. Inhibition of PGC1α using SR18292 diminishes the specific stemness by targeting FAO-independent and FAO-dependent OXPhos of ADM/PanINs and IPMNs, respectively.
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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.