ArticleBMC cancer2009
Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer.
Article in BMC cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer.Oncotarget · 2014Pooled it
- Helicobacter pylori-induced aberrant methylation of ID4 mediated by DNMT3B drives gastric cancer progression via DEC1-SHH signaling pathway.Cell death & disease · 2025Article
- Dysregulated miRNAs Targeting Adiponectin Signaling in Colorectal Cancer.International journal of molecular sciences · 2025Review
- The Critical Role of Inhibitor of Differentiation 4 in Breast Cancer: From Mammary Gland Development to Tumor Progression.Cancer medicine · 2025Review
- Article
- ID2 promotes tumor progression and metastasis in thyroid cancer.Endocrine · 2024Article
- Inhibitor of Differentiation 4 (ID4) represses mammary myoepithelial differentiation via inhibition of HEB.iScience · 2021Article
- Id4 Suppresses the Growth and Invasion of Colorectal Cancer HCT116 Cells through CK18-Related Inhibition of AKT and EMT Signaling.Journal of oncology · 2021Article
- The helix-loop-helix transcriptional regulator Id4 is required for terminal differentiation of luminal epithelial cells in the prostate.Oncoscience · 2021Article
- Wogonin reverses the drug resistance of chronic myelogenous leukemia cells to imatinib through CXCL12-CXCR4/7 axis in bone marrow microenvironment.Annals of translational medicine · 2020Article
- Article
- Epigenetic role of the nuclear factor NF-Y on ID gene family in endometrial tissues of women with endometriosis: a case control study.Reproductive biology and endocrinology : RB&E · 2019Article
- Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma.BioMed research international · 2019Article
- Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View.Frontiers in cell and developmental biology · 2019Article
- Inhibitor of DNA binding proteins: implications in human cancer progression and metastasis.American journal of translational research · 2018Review
- Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies.Journal of cellular and molecular medicine · 2017Article
- Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52.Molecular oncology · 2017Article
- Id4 promotes cell proliferation in hepatocellular carcinoma.Chinese journal of cancer · 2017Article
- The Id-protein family in developmental and cancer-associated pathways.Cell communication and signaling : CCS · 2017Review
- Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano-particle inhibits prostate cancer growth.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundInhibitor of differentiation 4 (Id4), a member of the Id gene family is also a dominant negative regulator of basic helix loop helix (bHLH) transcription factors. Some of the functions of Id4 appear to be unique as compared to its other family members Id1, Id2 and Id3. Loss of Id4 gene expression in many cancers in association with promoter hypermethylation has led to the proposal that Id4 may act as a tumor suppressor. In this study we provide functional evidence that Id4 indeed acts as a tumor suppressor and is part of a cancer associated epigenetic re-programming.
methodsData mining was used to demonstrate Id4 expression in prostate cancer. Methylation specific polymerase chain reaction (MSP) analysis was performed to understand molecular mechanisms associated with Id4 expression in prostate cancer cell lines. The effect of ectopic Id4 expression in DU145 cells was determined by cell cycle analysis (3H thymidine incorporation and FACS), expression of androgen receptor, p53 and cyclin dependent kinase inhibitors p27 and p21 by a combination of RT-PCR, real time-PCR, western blot and immuno-cytochemical analysis.
resultsId4 expression was down-regulated in prostate cancer. Id4 expression was also down-regulated in prostate cancer line DU145 due to promoter hyper-methylation. Ectopic Id4 expression in DU145 prostate cancer cell line led to increased apoptosis and decreased cell proliferation due in part by an S-phase arrest. In addition to S-phase arrest, ectopic Id4 expression in PC3 cells also resulted in prolonged G2/M phase. At the molecular level these changes were associated with increased androgen receptor (AR), p21, p27 and p53 expression in DU145 cells.
conclusionThe results suggest that Id4 acts directly as a tumor suppressor by influencing a hierarchy of cellular processes at multiple levels that leads to a decreased cell proliferation and change in morphology that is possibly mediated through induction of previously silenced tumor suppressors.
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