ArticleScience advances2019
BRK phosphorylates SMAD4 for proteasomal degradation and inhibits tumor suppressor FRK to control SNAIL, SLUG, and metastatic potential.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Discovery of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRK/PTK6 inhibitors.European journal of medicinal chemistry · 2025Article
- Prognostic impact of PTK6 expression in triple negative breast cancer.BMC women's health · 2023Article
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Oncogenic signaling-mediated regulation of chromatin during tumorigenesis.Cancer metastasis reviews · 2023Review
- Transforming growth factor-β signalling in tumour resistance to the anti-PD-(L)1 therapy: Updated.Journal of cellular and molecular medicine · 2023Review
- P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Correlation between Oxidative Stress and Transforming Growth Factor-Beta in Cancers.International journal of molecular sciences · 2021Review
- Multi-omics data integration reveals correlated regulatory features of triple negative breast cancer.Molecular omics · 2021Article
- Putting the BRK on breast cancer: From molecular target to therapeutics.Theranostics · 2021Review
- MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion.International journal of medical sciences · 2021Article
- Insights on Cancer Cell Inhibition, Subcellular Activities, and Kinase Profile of Phenylacetamides Pending 1Frontiers in pharmacology · 2021Article
- Deubiquitinase USP13 promotes extracellular matrix expression by stabilizing Smad4 in lung fibroblast cells.Translational research : the journal of laboratory and clinical medicine · 2020Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
The tumor-suppressing function of SMAD4 is frequently subverted during mammary tumorigenesis, leading to cancer growth, invasion, and metastasis. A long-standing concept is that SMAD4 is not regulated by phosphorylation but ubiquitination. Our search for signaling pathways regulated by breast tumor kinase (BRK), a nonreceptor protein tyrosine kinase that is up-regulated in ~80% of invasive ductal breast tumors, led us to find that BRK competitively binds and phosphorylates SMAD4 and regulates transforming growth factor-β/SMAD4 signaling pathway. A constitutively active BRK (BRK-Y447F) phosphorylates SMAD4, resulting in its recognition by the ubiquitin-proteasome system, which accelerates SMAD4 degradation. Activated BRK-mediated degradation of SMAD4 is associated with the repression of tumor suppressor gene
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