ArticleInternational journal of cancer2015
Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition.
Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- Hypoxia and lactate metabolism-related gene COL5A3 promotes triple negative breast cancer progression via DDR1/FAK/PI3K/AKT pathway.Biology direct · 2026Article
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation.Stem cell reports · 2025Article
- Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges.Journal of translational medicine · 2025Review
- Discoid Domain Receptors Signaling in Macrophages-Mediated Diseases.International journal of general medicine · 2025Review
- ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells.Autophagy · 2024Article
- Population dynamics of EMT elucidates the timing and distribution of phenotypic intra-tumoral heterogeneity.iScience · 2023Article
- MicroRNA-Gene Interactions Impacted by Toxic Metal(oid)s during EMT and Carcinogenesis.Cancers · 2022Review
- DDR2 coordinates EMT and metabolic reprogramming as a shared effector of FOXQ1 and SNAI1.Cancer research communications · 2022Article
- Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease.Frontiers in pharmacology · 2022Review
- A curcumin analog CA-5f inhibits urokinase-type plasminogen activator and invasive phenotype of triple-negative breast cancer cells.Toxicological research · 2022Article
- Complex roles of discoidin domain receptor tyrosine kinases in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Article
- The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development.Cancers · 2021Review
- Collagen and Discoidin Domain Receptor 1 Partnership: A Multifaceted Role in the Regulation of Breast Carcinoma Cell Phenotype.Frontiers in cell and developmental biology · 2021Review
- Recent Advances in the Role of Discoidin Domain Receptor Tyrosine Kinase 1 and Discoidin Domain Receptor Tyrosine Kinase 2 in Breast and Ovarian Cancer.Frontiers in cell and developmental biology · 2021Review
- Ras Signaling in Breast Cancer.Advances in experimental medicine and biology · 2021Article
- Targeting Discoidin Domain Receptor 1 (DDR1) Signaling and Its Crosstalk with βInternational journal of molecular sciences · 2020Article
- AR-dependent phosphorylation and phospho-proteome targets in prostate cancer.Endocrine-related cancer · 2020Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The epithelial-to-mesenchymal transition (EMT) process allows carcinoma cells to dissociate from the primary tumor thereby facilitating tumor cell invasion and metastasis. Ras-dependent hyperactive signaling is commonly associated with tumorigenesis, invasion, EMT, and metastasis. However, the downstream effectors by which Ras regulates EMT remain ill defined. In this study, we show that the H-Ras pathway leads to mesenchymal-like phenotypic changes in human breast epithelial cells by controlling the ZEB1/microRNA-200c axis. Moreover, H-Ras suppresses the expression of the discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase, via ZEB1, thus identifying ZEB1 as a novel transcriptional repressor of DDR1. Mutation studies on the putative promoter of the DDR1 gene revealed that bipartite Z- and E-box elements play a key role in transcriptional repression of DDR1 in Hs578T and MDA-MB-231 breast carcinoma cell lines by ZEB1. Furthermore, we found an inverse correlation between ZEB1 and DDR1 expression in various cancer cell lines and in human breast carcinoma tissues. Consistently, overexpression of DDR1 reduced the invasive phenotype of mesenchymal-like triple-negative breast cancer cells in 3D cultures and in vivo. Thus, ZEB1's role in maintenance of EMT in breast carcinoma cells is mediated in part by its ability to suppress DDR1 expression and consequently contribute to the activation of the invasive phenotype. Taken together, our results unveil a novel H-Ras/ZEB1/DDR1 network that contributes to breast cancer progression in triple-negative breast cancers.
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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.