ArticleMolecular cancer2014
Profilin-1 suppresses tumorigenicity in pancreatic cancer through regulation of the SIRT3-HIF1α axis.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- A Malignant Subpopulation of H2AFZ+ Cells Interacts with Myeloid Cells to Promote an Anti-inflammatory Microenvironment and Drive Hepatic Metastasis, Revealing an Immunotherapeutic Strategy for Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Profilin-1 Deficiency Activates STING to Drive T Cell-Mediated Anti-Tumor Immunity in Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- Profilin and Its Isoforms: Unravelling the Functional Diversity Across Life Forms.Current protein & peptide science · 2026Review
- Circ_0000972 Inhibits Hepatocellular Carcinoma Cell Stemness by Targeting miR-96-5p/PFN1.Biochemical genetics · 2025Article
- Integrated spectroscopic and morphological analyses reveal cellular shifts in gene-silenced melanoma CSCs.Scientific reports · 2025Article
- Article
- PFN1 Knockdown Aggravates Mitophagy to Retard Lung Adenocarcinoma Initiation and M2 Macrophage Polarization.Molecular biotechnology · 2025Article
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism.BMC complementary medicine and therapies · 2024Article
- SIRT3 Activation a Promise in Drug Development? New Insights into SIRT3 Biology and Its Implications on the Drug Discovery Process.Journal of medicinal chemistry · 2024Review
- Mitochondrial sirtuins: Energy dynamics and cancer metabolism.Molecules and cells · 2024Review
- Exploring Molecular Alterations in Breast Cancer Among Indian Women Using Label-Free Quantitative Serum Proteomics.Biochemistry research international · 2024Article
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- Profilin1 Promotes Renal Tubular Epithelial Cell Apoptosis in Diabetic Nephropathy Through the Hedgehog Signaling Pathway.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.The Kaohsiung journal of medical sciences · 2022Article
- Cancer metabolism challenges genomic instability and clonal evolution as therapeutic targets.Cancer science · 2022Review
- Unravelling theMolecules (Basel, Switzerland) · 2022Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor cells exhibit abnormal actin remodeling profiles, which involve the altered expressions of several important actin-binding proteins. Profilin1 (Pfn1), originally identified as an actin-associated protein, has been linked to several human malignancies. Our recent studies suggested that Pfn1 facilitates apoptosis in pancreatic cancer cells. Here, we investigated the exact role of Profilin1 (Pfn1) in pancreatic adenocarcinoma (PDAC) and the underlying mechanisms.
methodsPfn1 protein expression in PDAC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing PDAC tumor tissue and corresponding normal tissue samples from 72 patients. The effect of Pfn1 expression on cancer proliferation was assessed in cells by up- and down-regulation of Pfn1 in vitro and in vivo. Immunoprecipitation and mass spectrometry were used to identify the Pfn1-associated proteins and potential pathways.
resultsPfn1 was downregulated in clinical pancreatic adenocarcinoma specimens compared with the surrounding benign tissues. Univariate survival analysis of the PDAC cohorts showed that low expression of Pfn1 was significantly correlated with shortened patient survival (mean 14.2 months versus 20.9 months, P < 0.05). Restoration of Pfn1 in pancreatic cancer cells with low endogenous Pfn1 expression resulted in a nontumorigenic phenotype, suggesting that Pfn1 may be a negative regulator of pancreatic cancer progression. Overexpression of Pfn1 in vivo decreased the tumor volume in orthotopic xenograft nude mice models. Pfn1 upregulated the expression of SIRT3, leading to HIF1α destabilization. This data revealed that aberrant Pfn1 expression contributes to pancreatic cancer progression.
conclusionsOur data suggest that Pfn1 is a tumor suppressor in pancreatic cancer that acts via a novel mechanism of regulating the SIRT3-HIF1α axis, independently of its cytoskeleton-related activity.
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