ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
Cbl-b accelerates trypsin-induced cell detachment through ubiquitination and degradation of proline-rich tyrosine kinase 2.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Functional sQTLs regulating PTK2B exon 31 splicing uncover an RNA-dependent modulation of its kinase activity and cellular phenotype.Cell communication and signaling : CCS · 2026Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Reduced Proline-Rich Tyrosine Kinase 2 Promotes Tumor Metastasis by Activating Epithelial-Mesenchymal Transition in Colorectal Cancer.Digestive diseases and sciences · 2024Article
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypsin is a digestive enzyme that is widely used for cell detachment, which is the first stage of tumor metastasis. Recent studies show that adhesion-related kinases are involved in cell detachment. Proline-rich tyrosine kinase 2 (Pyk2) is a crucial kinase in the regulation of cell adhesion and detachment. However, the effect of Pyk2 on cell detachment is controversial. In the present study, we found that Pyk2 expression was rapidly decreased after trypsin treatment in gastric cancer, breast cancer, colon cancer, lung cancer, and human gastric epithelial cells. Knockdown of Pyk2 accelerated cell detachment. Furthermore, lysosome inhibitor NH4CL suppressed cell detachment and increased ubiquitination of Pyk2. Cbl-b is a type of E3 ubiquitin ligase that interacted with Pyk2, reduced the expression of Pyk2, and promoted trypsin-induced degradation of Pyk2. These findings suggest that Cbl-b promoted cell detachment through mono-ubiquitination of Pyk2. Our data provide a new insight into the role of Cbl-b in cell detachment.
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Registered trials
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