ArticleCancer cell international2023
Blockage of retinoic acid signaling via RARγ suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression of the G1-S phase.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- The role of RARG in solid tumor progression and therapeutic potential.Discover oncology · 2026Review
- The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026Review
- The Emerging Oncogenic Role of RARγ: From Stem Cell Regulation to a Potential Cancer Therapy.International journal of molecular sciences · 2025Review
- METTL14 regulates proliferation and differentiation of duck myoblasts through targeting MiR-133b.PloS one · 2025Article
- Targeting Androgen, Thyroid Hormone, and Vitamin A and D Receptors to Treat Prostate Cancer.International journal of molecular sciences · 2024Review
- Deregulation of All-International journal of molecular sciences · 2023Review
- Targeting the Retinoic Acid Pathway to Eradicate Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Retinoic acid receptor regulation of decision-making for cell differentiation.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundOur study and several studies have reported that in some cancers, including pancreatic ductal adenocarcinoma (PDAC), the expression of squamous lineage markers, such as esophagus-tissue-specific genes, correlated with a poor prognosis. However, the mechanism by which the acquisition of squamous lineage phenotypes leads to a poor prognosis remains unclear. We previously reported that retinoic acid signaling via retinoic acid receptor γ (RARγ signaling) determines the differentiation lineage into the esophageal squamous epithelium. These findings hypothesized that the activation of RARγ signaling contributed to acquiring squamous lineage phenotypes and malignant behavior in PDAC.
methodsThis study utilized public databases and immunostaining of surgical specimens to examine RARγ expression in PDAC. We evaluated the function of RARγ signaling by inhibitors and siRNA knockdown using a PDAC cell line and patient-derived PDAC organoids. The mechanism of the tumor-suppressive effects by blocking RARγ signaling was examined by a cell cycle analysis, apoptosis assays, RNA sequencing and Western blotting.
resultsRARγ expression in pancreatic intraepithelial neoplasia (PanIN) and PDAC was higher than that in the normal pancreatic duct. Its expression correlated with a poor patient prognosis in PDAC. In PDAC cell lines, blockade of RARγ signaling suppressed cell proliferation by inducing cell cycle arrest in the G1 phase without causing apoptosis. We demonstrated that blocking RARγ signaling upregulated p21 and p27 and downregulated many cell cycle genes, including cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6. Furthermore, using patient-derived PDAC organoids, we confirmed the tumor-suppressive effect of RARγ inhibition and indicated the synergistic effects of RARγ inhibition with gemcitabine.
conclusionsThis study clarified the function of RARγ signaling in PDAC progression and demonstrated the tumor-suppressive effect of selective blockade of RARγ signaling against PDAC. These results suggest that RARγ signaling might be a new therapeutic target for PDAC.
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