ArticleOncotarget2016
Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Unraveling the Molecular Mechanisms of Glioma Recurrence: A Study Integrating Single-Cell and Spatial Transcriptomics.Annals of clinical and translational neurology · 2026Article
- Epigenetic regulation of breast ductal carcinoma in situ by miR-217 through DNMT1 and Hedgehog-GLI pathway.Journal of cell communication and signaling · 2025Article
- AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival.Biochemistry and biophysics reports · 2025Article
- Article
- ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer.EMBO reports · 2022Article
- Obesity-linked circular RNA circTshz2-2 regulates the neuronal cell cycle and spatial memory in the brain.Molecular psychiatry · 2021Article
- Early-life social experience affects offspring DNA methylation and later life stress phenotype.Nature communications · 2021Article
- TSHZ2 is an EGF-regulated tumor suppressor that binds to the cytokinesis regulator PRC1 and inhibits metastasis.Science signaling · 2021Article
- XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment.Science advances · 2021Article
- RNA-Seq analysis reveals gene expression changes induced by IL-6 trans-signaling activation in retinal endothelial cells.Cytokine · 2021Article
- The phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of estrone and bisphenol A in zebrafish.The Science of the total environment · 2021Article
- Overexpression of Teashirt Homolog 2 suppresses cell proliferation and predicts the favorable survival of Lung Adenocarcinoma.International journal of medical sciences · 2021Observational
- Review
- AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways.Journal of oncology · 2020Review
- Identification of NovelFrontiers in genetics · 2020Article
- Identification of Metastasis-Associated Genes in Triple-Negative Breast Cancer Using Weighted Gene Co-expression Network Analysis.Evolutionary bioinformatics online · 2020Article
- The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.Oncogene · 2019Article
- Master Regulators of Signaling Pathways: An Application to the Analysis of Gene Regulation in Breast Cancer.Frontiers in genetics · 2019Article
- Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease.PloS one · 2019Article
- C-Terminal Binding Protein is Involved in Promoting to the Carcinogenesis of Human Glioma.Molecular neurobiology · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1.
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