ArticleOncogene2012
SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
186 citing papers in PubMed, 1 synthesis or guideline pooled it, 310 citations in OpenAlex.
- Prognostic and clinical value of Sirt1 expression in gastric cancer: A systematic meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016Pooled it
- Ticagrelor IncreasesInternational journal of molecular sciences · 2020Trial
- A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.The Journal of experimental medicine · 2026Article
- Targeting Sirtuins in Thyroid Cancer: Mechanisms, Drug Development, and Emerging Roles in Tumor Immunity and Ferroptosis.Cancers · 2026Review
- Article
- Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.Molecular and cellular biochemistry · 2025Review
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Article
- Cancer, metastasis, and the epigenome.Molecular cancer · 2024Review
- Machine learning identifies activation of RUNX/AP-1 as drivers of mesenchymal and fibrotic regulatory programs in gastric cancer.Genome research · 2024Article
- SIRT1 mediates breast cancer development and tumorigenesis controlled by estrogen-related receptor β.Breast cancer (Tokyo, Japan) · 2024Article
- The therapeutic potential of targeting the CHD protein family in cancer.Pharmacology & therapeutics · 2024Review
- The role of SIRT1 in autophagy and drug resistance: unveiling new targets and potential biomarkers in cancer therapy.Frontiers in pharmacology · 2024Review
- Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics.Cancer metastasis reviews · 2023Review
- TCR Pathway Mutations in Mature T Cell Lymphomas.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft.Cancers · 2023Article
- NKX3.1 Expression Contributes to Epithelial-Mesenchymal Transition of Prostate Cancer Cells.ACS omega · 2023Article
- Oligometastases: Characterizing the Role of Epigenetic Regulation of Epithelial-Mesenchymal Transition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
126 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The epithelial-to-mesenchymal transition (EMT) is a crucial program for the invasion and metastasis of epithelial tumors that involves loss of cell-cell adhesion and increased cell mobility; however, mechanisms underlying this transition are not fully elucidated. Here, we propose a novel mechanism through which the nicotinamide adenine dinucleotide-dependent histone deacetylase SIRT1 regulates EMT in prostate cancer cells through cooperation with the EMT inducing transcription factor ZEB1. We found that forced expression of SIRT1 in non-transformed PZ-HPV-7 prostate epithelial cells disrupts the epithelial morphology concomitant with decreased expression of the epithelial marker, E-cadherin, and increased expression of mesenchymal markers. In contrast, silencing SIRT1 in metastatic prostate tumor cells restores cell-cell adhesion and induces a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. We also found that SIRT1 has a physiologically relevant role in endogenous EMT induced by EGF signaling in prostate cancer cells. We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1. Specifically, we show that SIRT1 silencing reduces expression of ZEB1 and that SIRT1 is recruited to the E-cadherin proximal promoter by ZEB1 to deacetylate histone H3 and to reduce binding of RNA polymerase II, ultimately suppressing E-cadherin transcription. We thus identify a necessary role for ZEB1 in SIRT1-mediated EMT. Finally, we show that reduction of SIRT1 decreases prostate cancer cell migration in vitro and metastasis in vivo in immunodeficient mice, which is largely independent of any general effects of SIRT1 on prostate cancer growth and survival. We therefore identify SIRT1 as a positive regulator of EMT and metastatic growth of prostate cancer cells and our findings implicate overexpressed SIRT1 as a potential therapeutic target to reverse EMT and to prevent prostate cancer progression.
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Registered trials
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.