ArticleOncogene2024
N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Ferroptosis Suppression by the MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
- The KRT15 and KRT81 complex promotes lenvatinib resistance in thyroid cancer by upregulating DGKB mediated lipid metabolism.Scientific reports · 2026Article
- Erianin facilitates pyroptosis in endometrial cancer via targeting m6A reader YTHDF1.Chinese medicine · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- PSMD14-Mediated LDHA Deubiquitination Upregulates ACLY Expression via H3K18 Lactylation to Promote Lipid Synthesis and Pancreatic Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- Article
- Cross-tissue transcriptome-wide analysis reveals novel insights into thyroid cancer etiology.Discover oncology · 2025Article
- Article
- Recent Findings in N6-Methyladenosine Modification and Significance in Pancreatic Cancer.Cancer medicine · 2025Review
- Biological roles of enhancer RNA m6A modification and its implications in cancer.Cell communication and signaling : CCS · 2025Review
- Targeting lipid metabolism: novel insights and therapeutic advances in pancreatic cancer treatment.Lipids in health and disease · 2025Review
- Matrix stiffness boosts PDAC chemoresistance via SCD1-dependent lipid metabolic reprogramming.Regenerative biomaterials · 2025Article
- Research progress on m6A and drug resistance in gastrointestinal tumors.Frontiers in pharmacology · 2025Review
- Natural Compounds as Potential Therapeutics for Pancreatic Cancer: A Narrative Review.Current drug metabolism · 2025Review
- The Mechanism and Latest Progress of m6A Methylation in the Progression of Pancreatic Cancer.International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.
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