ArticlePloS one2012
Down-regulation of HtrA1 activates the epithelial-mesenchymal transition and ATM DNA damage response pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review.Molecular diagnosis & therapy · 2024Pooled it
- Fibronectin Is a Likely Therapeutic Target Shared by Oral and Breast Carcinomas.International journal of molecular sciences · 2026Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- SUMO Antibody Validation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- HTRA1 expression is associated with immune-cell infiltration and survival in breast cancer.Translational cancer research · 2023Article
- Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity.The American journal of pathology · 2023Article
- Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles.Human genomics · 2022Article
- TGF-β/Smad Signalling Activation by HTRA1 Regulates the Function of Human Lens Epithelial Cells and Its Mechanism in Posterior Subcapsular Congenital Cataract.International journal of molecular sciences · 2022Article
- High temperature requirement A1 in cancer: biomarker and therapeutic target.Cancer cell international · 2021Review
- Review
- Characterization of a novel HDAC/RXR/HtrA1 signaling axis as a novel target to overcome cisplatin resistance in human non-small cell lung cancer.Molecular cancer · 2020Article
- Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer.iScience · 2020Article
- Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers.Cell proliferation · 2020Review
- A Six-Epithelial-Mesenchymal Transition Gene Signature May Predict Metastasis of Triple-Negative Breast Cancer.OncoTargets and therapy · 2020Article
- In Vitro Models for Studying Invasive Transitions of Ductal Carcinoma In Situ.Journal of mammary gland biology and neoplasia · 2019Review
- BMP-Responsive Protease HtrA1 Is Differentially Expressed in Astrocytes and Regulates Astrocytic Development and Injury Response.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.Pathology oncology research : POR · 2017Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of the serine protease HtrA1 is decreased or abrogated in a variety of human primary cancers, and higher levels of HtrA1 expression are directly related to better response to chemotherapeutics. However, the precise mechanisms leading to HtrA1 down regulation during malignant transformation are unclear. To investigate HtrA1 gene regulation in breast cancer, we characterized expression in primary breast tissues and seven human breast epithelial cell lines, including two non-tumorigenic cell lines. In human breast tissues, HtrA1 expression was prominent in normal ductal glands. In DCIS and in invasive cancers, HtrA1 expression was greatly reduced or lost entirely. HtrA1 staining was also reduced in all of the human breast cancer cell lines, compared with the normal tissue and non-tumorigenic cell line controls. Loss of HtrA1 gene expression was attributable primarily to epigenetic silencing mechanisms, with different mechanisms operative in the various cell lines. To mechanistically examine the functional consequences of HtrA1 loss, we stably reduced and/or overexpressed HtrA1 in the non-tumorigenic MCF10A cell line. Reduction of HtrA1 levels resulted in the epithelial-to-mesenchymal transition with acquisition of mesenchymal phenotypic characteristics, including increased growth rate, migration, and invasion, as well as expression of mesenchymal biomarkers. A concomitant decrease in expression of epithelial biomarkers and all microRNA 200 family members was also observed. Moreover, reduction of HtrA1 expression resulted in activation of the ATM and DNA damage response, whereas overexpression of HtrA1 prevented this activation. Collectively, these results suggest that HtrA1 may function as a tumor suppressor by controlling the epithelial-to-mesenchymal transition, and may function in chemotherapeutic responsiveness by mediating DNA damage response pathways.
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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.