ArticleMolecular cancer research : MCR2021
Breast Tumor Kinase (Brk/PTK6) Mediates Advanced Cancer Phenotypes via SH2-Domain Dependent Activation of RhoA and Aryl Hydrocarbon Receptor (AhR) Signaling.
Article in Molecular cancer research : MCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Establishment of Breast Cancer Organoids: A Systematic Review and Meta-Analysis.International journal of breast cancer · 2026Article
- Discovery of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRK/PTK6 inhibitors.European journal of medicinal chemistry · 2025Article
- A PROTAC degrader suppresses oncogenic functions of PTK6, inducing apoptosis of breast cancer cells.Cell chemical biology · 2025Article
- In Silico Screening of Multi-Domain Targeted Inhibitors for PTK6: A Strategy Integrating Drug Repurposing and Consensus Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Prognostic impact of PTK6 expression in triple negative breast cancer.BMC women's health · 2023Article
- Aryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey.Molecules (Basel, Switzerland) · 2023Review
- Review
- Review
- Sabizabulin, a Potent Orally Bioavailable Colchicine Binding Site Agent, Suppresses HER2+ Breast Cancer and Metastasis.Cancers · 2022Article
- Interference of PTK6/GAB1 signaling inhibits cell proliferation, invasion, and migration of cervical cancer cells.Molecular medicine reports · 2022Article
- Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2022Article
- Comprehensive Analysis Reveals PTK6 as a Prognostic Biomarker Involved in the Immunosuppressive Microenvironment in Breast Cancer.Journal of immunology research · 2022Article
- An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.Handbook of experimental pharmacology · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine kinase 6 (PTK6; also called Brk) is overexpressed in 86% of patients with breast cancer; high PTK6 expression predicts poor outcome. We reported PTK6 induction by HIF/GR complexes in response to either cellular or host stress. However, PTK6-driven signaling events in the context of triple-negative breast cancer (TNBC) remain undefined. In a mouse model of TNBC, manipulation of PTK6 levels (i.e., via knock-out or add-back) had little effect on primary tumor volume, but altered lung metastasis. To delineate the mechanisms of PTK6 downstream signaling, we created kinase-dead (KM) and kinase-intact domain structure mutants of PTK6 via in-frame deletions of the N-terminal SH3 or SH2 domains. While the PTK6 kinase domain contributed to soft-agar colony formation, PTK6 kinase activity was entirely dispensable for cell migration. Specifically, TNBC models expressing a PTK6 variant lacking the SH2 domain (SH2-del PTK6) were unresponsive to growth factor-stimulated cell motility relative to SH3-del, KM, or wild-type PTK6 controls. Reverse-phase protein array revealed that while intact PTK6 mediates spheroid formation via p38 MAPK signaling, the SH2 domain of PTK6 limits this biology, and instead mediates TNBC cell motility via activation of the RhoA and/or AhR signaling pathways. Inhibition of RhoA and/or AhR blocked TNBC cell migration as well as the branching/invasive morphology of PTK6
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