ArticleOncogene2021
OSR1 phosphorylates the Smad2/3 linker region and induces TGF-β1 autocrine to promote EMT and metastasis in breast cancer.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
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- Characterization of Proteome Features in Patients With Aortic Stenosis Using Data-Independent Acquisition-Based Proteomic Analysis.Korean circulation journal · 2026Article
- WNK1 promotes head and neck squamous cell carcinoma progression through activation of NF-κB signaling pathway.Discover oncology · 2025Article
- Expanding the druggable zinc-finger proteome defines properties of drug-induced degradation.Molecular cell · 2025Article
- Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential.ACS pharmacology & translational science · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
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- Identification and validation of DNA methylation-driven gene OSR1 as a novel tumor suppressor for the diagnosis and prognosis of breast cancer.Frontiers in genetics · 2025Article
- Kinome-wide CRISPR-Cas9 screens revealedBiochemistry and biophysics reports · 2024Article
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- Oral Microbiome and CPT1A Function in Fatty Acid Metabolism in Oral Cancer.International journal of molecular sciences · 2024Article
- The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.Frontiers in toxicology · 2024Article
- Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.BMC cancer · 2023Article
- Tripartite motif-containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis.Journal of cell communication and signaling · 2023Article
- ESRRB Inhibits the TGFβ Signaling Pathway to Drive Cell Proliferation in Cervical Cancer.Cancer research · 2023Article
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
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- Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo.International journal of molecular sciences · 2023Article
- The current status and future of PD-L1 in liver cancer.Frontiers in immunology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress-responsive kinase 1 (OSR1) plays a critical role in multiple carcinogenic signal pathways, and its overexpression has been found in various types of cancer; however, the pathophysiological role of OSR1 in breast cancer has not been evaluated. This study aims to elaborate on the role of OSR1 in breast cancer metastasis and the specific regulatory mechanism. Our results showed that OSR1 mRNA and protein were upregulated in both human breast cancer samples and cell lines. Moreover, phosphorylated OSR1 (p-OSR1) was an independent poor prognostic indicator in patients with breast cancer. OSR1 upregulation induced epithelial-to-mesenchymal transition (EMT) in normal and malignant mammary epithelial cells with the increasing metastatic capacity. In contrast, deleting OSR1 in aggressive breast cancer cells inhibited these phenotypes. OSR1 is the critical activator for transcription factors of EMT. Mechanistically, we found that OSR1 can directly interact and phosphorylate the linker region of Smad2 at Thr220 and Smad3 at Thr179. Phosphorylated Smad2/3 translocated into the nucleus to enhance transforming growth factor-β1 (TGF-β1) autocrine signalling and increase the transcription of EMT regulators. Importantly, interruption of the OSR1-Smad2/3-TGF-β1 signalling axis elicited a robust anti-EMT and anti-metastatic effect in vitro and in vivo. Taken together, we conclude that OSR1-mediated Smad2/3-TGF-β1 signalling promotes EMT and metastasis representing a promising therapeutic target in breast cancer treatment.
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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.