ArticleOncogene2012
Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Protein tyrosine kinase-6 is post-translationally regulated by arginine methylation and ubiquitination.Cell death & disease · 2026Article
- PTK6 drives HNRNPH1 phase separation to activate autophagy and suppress apoptosis in colorectal cancer.Autophagy · 2025Article
- The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms.Biomedicines · 2024Review
- Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications.Exploration of targeted anti-tumor therapy · 2024Review
- An EGCG Derivative in Combination with Nimotuzumab for the Treatment of Wild-Type EGFR NSCLC.International journal of molecular sciences · 2023Article
- Review
- PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.Cell death & disease · 2023Article
- Review
- Putting the BRK on breast cancer: From molecular target to therapeutics.Theranostics · 2021Review
- Targeting protein tyrosine kinase 6 in cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Identification of Signatures of Prognosis Prediction for Melanoma Using a Hypoxia Score.Frontiers in genetics · 2020Article
- Long Noncoding RNA LINC01485 Promotes Tumor Growth and Migration via Inhibiting EGFR Ubiquitination and Activating EGFR/Akt Signaling in Gastric Cancer.OncoTargets and therapy · 2020Article
- Protein tyrosine kinase 6 signaling in prostate cancer.American journal of clinical and experimental urology · 2020Review
- Vemurafenib Inhibits Active PTK6 inMolecular cancer therapeutics · 2019Article
- Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis.Molecular cancer research : MCR · 2018Article
- Functional cooperation between HIF-1α and c-Jun in mediating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR.Lung cancer (Amsterdam, Netherlands) · 2018Article
- STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization.The Journal of biological chemistry · 2017Article
- The associated pyrazolopyrimidines PP1 and PP2 inhibit protein tyrosine kinase 6 activity and suppress breast cancer cell proliferation.Oncology letters · 2017Article
- The marine-derived pachycladin diterpenoids as novel inhibitors of wild-type and mutant EGFR.Biochemical pharmacology · 2017Article
- Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer.Cancer research · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR)-mediated cell signaling is critical for mammary epithelial cell growth and survival; however, targeting EGFR has shown no or only minimal therapeutic benefit in patients with breast cancer. Here, we report a novel regulatory mechanism of EGFR signaling that may explain the low response rates. We found that breast tumor kinase (Brk)/protein-tyrosine kinase 6 (PTK6), a nonreceptor protein-tyrosine kinase highly expressed in most human breast tumors, interacted with EGFR and sustained ligand-induced EGFR signaling. We demonstrate that Brk inhibits ligand-induced EGFR degradation through uncoupling activated EGFR from casitas B-lineage lymphoma-mediated EGFR ubiquitination. In addition, upon activation by EGFR, Brk directly phosphorylated Y845 in the EGFR kinase domain, thereby further potentiating EGFR kinase activity. Experimental elevation of Brk conferred resistance of breast cancer cells to cetuximab (an EGFR-blocking antibody)-induced inhibition of cell signaling and proliferation, whereas knockdown of Brk sensitized the cells to cetuximab by inducing apoptosis. Our findings reveal a previously unknown role of Brk in EGFR-targeted therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.