ArticleOncotarget2015
PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- The focal adhesion kinases regulate leptin action and the weight reducing effect of HDAC6 inhibition.Nature communications · 2026Article
- Inhibition of HER2 signaling and breast cancer cell growth with a novel antibody targeting HER2 ECD III/IV.PloS one · 2026Article
- Discovery and Evaluation of Novel Sulfonamide Derivatives Targeting Aromatase in ER+ Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.Acta pharmacologica Sinica · 2024Article
- CAR-mediated targeting of NK cells overcomes tumor immune escape caused by ICAM-1 downregulation.Journal for immunotherapy of cancer · 2024Article
- Tyrphostin A9 attenuates glioblastoma growth by suppressing PYK2/EGFR-ERK signaling pathway.Journal of neuro-oncology · 2023Article
- Protein dynamics at invadopodia control invasion-migration transitions in melanoma cells.Cell death & disease · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Mouse Modeling Dissecting Macrophage-Breast Cancer Communication Uncovered Roles of PYK2 in Macrophage Recruitment and Breast Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation.Cancer immunology, immunotherapy : CII · 2021Article
- Pyk2 level is a novel prognostic marker for patients with esophageal squamous cell carcinoma after radical surgery.Virchows Archiv : an international journal of pathology · 2021Article
- Review
- Heregulin Drives Endocrine Resistance by Altering IL-8 Expression in ER-Positive Breast Cancer.International journal of molecular sciences · 2020Article
- Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor.Cancers · 2020Article
- PYK2 promotes HER2-positive breast cancer invasion.Journal of experimental & clinical cancer research : CR · 2019Article
- Pyk2 promotes tumor progression in renal cell carcinoma.Oncology letters · 2018Article
- Review
- Expression of the serotonin receptor 2B in uveal melanoma and effects of an antagonist on cell lines.Clinical & experimental metastasis · 2018Article
- Pyk2 and FAK differentially regulate invadopodia formation and function in breast cancer cells.The Journal of cell biology · 2018Article
- Significance of PYK2 level as a prognosis predictor in patients with colon adenocarcinoma after surgical resection.OncoTargets and therapy · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of ErbB family members in breast cancer progression and metastasis has been demonstrated by many studies. However, the downstream effectors that mediate their migratory and invasive responses have not been fully explored. In this study, we show that the non-receptor tyrosine kinase PYK2 is a key effector of EGFR and HER2 signaling in human breast carcinoma. We found that PYK2 is activated by both EGF and heregulin (HRG) in breast cancer cells, and positively regulates EGF/HRG-induced cell spreading, migration and invasion. PYK2 depletion markedly affects ERK1/2 and STAT3 phosphorylation in response to EGF/HRG as well as to IL8 treatment. Importantly, PYK2 depletion also reduced EGF/HRG-induced MMP9 and IL8 transcription, while IL8 inhibition abrogated EGF-induced MMP9 transcription and attenuated cell invasion. IL8, which is transcriptionally regulated by STAT3 and induces PYK2 activation, prolonged EGF-induced PYK2, STAT3 and ERK1/2 phosphorylation suggesting that IL8 acts through an autocrine loop to reinforce EGF-induced signals. Collectively our studies suggest that PYK2 is a common downstream effector of ErbB and IL8 receptors, and that PYK2 integrates their signaling pathways through a positive feedback loop to potentiate breast cancer invasion. Hence, PYK2 could be a potential therapeutic target for a subset of breast cancer patients.
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