ArticleCell death & disease2021
Cancer-associated fibroblasts-mediated ATF4 expression promotes malignancy and gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- ATF4 and FGFR4 cooperatively support thyroid cancer progression and CAF-associated tumor-promoting features.Endocrine · 2026Article
- The CD49b (ITGA2) collagen receptor excludes CD8iScience · 2026Article
- Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer.medRxiv : the preprint server for health sciences · 2026Article
- CAF-derived PTGDS drives pancreatic cancer neuroendocrine differentiation and chemoresistance via PAQR9-MAPK.Oncogenesis · 2026Article
- USP10 promotes cell proliferation and gemcitabine resistance in pancreatic cancer by the regulation of IGF2BP3-STEAP3.Oncogene · 2026Article
- Cancer-associated fibroblasts: enablers of tumor drug resistance.Journal of translational medicine · 2026Review
- A positive feedback loop between SERPINH1 and MMP-9/TGF-β1 promotes lung adenocarcinoma progression.Cell death and differentiation · 2026Article
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- The Level of a Short Form of Multidrug Resistance-Associated Protein 1 Is Elevated in Plasma Small Extracellular Vesicles Derived From Patients With Pancreatic Ductal Adenocarcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche.Nature communications · 2025Article
- Exploratory Study on Nanoparticle Co-Delivery of Temozolomide and Ligustilide for Enhanced Brain Tumor Therapy.Pharmaceutics · 2025Article
- Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer.Neoplasia (New York, N.Y.) · 2025Article
- An Overview of Research Advances in Oncology Regarding the Transcription Factor ATF4.Current drug targets · 2025Review
- PARP9 drives the malignant progression of pancreatic cancer cells by regulating apoptosis, DNA damage, and multidrug efflux systems.Frontiers in cell and developmental biology · 2025Article
- Matrix stiffness influences drug resistance to gemcitabine analog and AZD 1775 combination in PDAC organoids.PloS one · 2025Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- TGF-β Signaling Loop in Pancreatic Ductal Adenocarcinoma Activates Fibroblasts and Increases Tumor Cell Aggressiveness.Cancers · 2024Article
- Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).International journal of oncology · 2024Review
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) contribute to malignant progression and chemoresistance in pancreatic ductal adenocarcinoma (PDAC). However, little is known about the underlying mechanism. In this study, we investigated the potential role and mechanisms of activating transcription factor 4 (ATF4) in CAFs-induced malignancy and gemcitabine resistance. We demonstrated that ATF4 is overexpressed in PDAC and associated with a poor prognosis. Silencing ATF4 expression decreased proliferation, colony formation, migration, gemcitabine sensitivity, and sphere formation. Subsequently, we revealed that CAFs secrete TGF-β1 to upregulate the expression of ATF4 in PDAC cells via the SMAD2/3 pathway and induce cancer progression, cancer stemness, and gemcitabine resistance. Furthermore, we demonstrated that ATF4 directly binds to the ABCC1 promoter region to activate transcription. In summary, these data demonstrate that CAFs contribute to malignancy and gemcitabine resistance in PDAC by upregulating the expression of ATF4 via the TGF-β1/SMAD2/3 axis and highlight that ATF4 is an attractive therapeutic target for combating gemcitabine resistance in PDAC.
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