ArticleComputational and structural biotechnology journal2024
Smad4 regulates TGF-β1-mediated hedgehog activation to promote epithelial-to-mesenchymal transition in pancreatic cancer cells by suppressing Gli1 activity.
Article in Computational and structural biotechnology journal, 2024. 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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12 citing papers in PubMed, 14 citations in OpenAlex.
- ARHI as a key regulator of EMT and metastasis in pancreatic cancer via the Notch-1 pathway.Human genetics · 2026Article
- Knowledge Discovery and Drug-Repurposing Framework for Pancreatic Ductal Adenocarcinoma: Molecular Networking and Computational Docking.Computational and structural biotechnology journal · 2026Article
- MUC13-Associated Molecular Interactome in Pancreatic Cancer.Computational and structural biotechnology journal · 2026Article
- Ethyl Acetate Extract from Wenxia Formula (WFEA) Attenuates Immunosuppression in Lung Cancer by Inhibiting Treg DifferentiationCurrent topics in medicinal chemistry · 2026Article
- The central role of EMT in tumor progression: mechanistic drivers, biomarker discovery, and therapeutic horizons.Frontiers in pharmacology · 2026Review
- The type I collagen paradox in PDAC progression: microenvironmental protector turned tumor accomplice.Journal of translational medicine · 2025Review
- Recent advances and challenges in colorectal cancer: From molecular research to treatment.World journal of gastroenterology · 2025Review
- Identification of a novel tRNA-derived small RNA fragment, tRF-16-2YU04DE, with the potential of inhibiting endometrial cancer progression.Medical oncology (Northwood, London, England) · 2025Article
- Nanomedicine in the Diagnosis and Treatment of Pancreatic Cancer.Pharmaceutics · 2025Review
- Computational investigation of stigmasterol as a potential therapeutic agent for cervical cancer: insights from density functional theory (DFT) and molecular docking studies.In silico pharmacology · 2025Article
- The role of SOX18 in nasopharyngeal carcinoma: implications for prognosis and therapy.American journal of translational research · 2025Article
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Authors and funding
11 authors at 2 institutions in 1 country.
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Abstract
Pancreatic cancer (PC) is an aggressive and metastatic gastrointestinal tumor with a poor prognosis. Persistent activation of the TGF-β/Smad signaling induces PC cell (PCC) invasion and infiltration via epithelial-to-mesenchymal transition (EMT). Hedgehog signaling is a crucial pathway for the development of PC via the transcription factors Gli1/2/3. This study aimed to investigate the underlying molecular mechanisms of action of hedgehog activation in TGF-β1-triggered EMT in PCCs (PANC-1 and BxPc-3). In addition, overexpression and shRNA techniques were used to evaluate the role of Smad4 in TGF-β1-treated PCCs. Our data showed that TGF-β1 promoted PCC invasion and infiltration via Smad2/3-dependent EMT. Hedgehog-Gli signaling axis in PCCs was activated upon TGF-β1 stimulation. Inhibition of hedgehog with cyclopamine effectively antagonized TGF-β1-induced EMT, thereby suggesting that the hedgehog signaling may act as a downstream cascade signaling of TGF-β1. As a key protein that assists the nuclear translocation of Smad2/3, Smad4 was highly expressed in PANC-1 cells, but not in BxPc-3 cells. Conversely, Gli1 expression was low in PANC-1 cells, but high in BxPc-3 cells. Furthermore, knockdown of Smad4 in PANC-1 cells by shRNA inhibited TGF-β1-mediated EMT and collagen deposition. Overexpression of Smad4 did not affect TGF-β1-mediated EMT due to the lack of significant increase in nuclear expression of Smad4. Importantly, Gli1 activity was upregulated by Smad4 knockdown in PANC-1 cells and downregulated by Smad4 overexpression in BxPc-3 cells, indicating that Gli1 may be a negative target protein downstream of Smad4. Thus, Smad4 regulates TGF-β1-mediated hedgehog activation to promote EMT in PCCs by suppressing Gli1 activity.
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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.