ArticlePloS one2011
Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- FAK and Pyk2: Paralogous Kinases with Opposing Roles in Vasculogenic Mimicry in Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Targeting the hydrophobic pockets of FAK/PYK2 FAT domain: a highly effective inhibitory strategy suppressing tumor growth and eliminating metastasis.Cell communication and signaling : CCS · 2025Article
- PYK2 promotes cell proliferation and epithelial-mesenchymal transition in endometriosis by phosphorylating Snail1.Molecular medicine (Cambridge, Mass.) · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Opposing Functions of Maspin Are Regulated by Its Subcellular Localization in Lung Squamous Cell Carcinoma Cells.Cancers · 2024Article
- Proline, a unique amino acid whose polymer, polyproline II helix, and its analogues are involved in many biological processes: a review.Amino acids · 2024Review
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Physiological and pathological roles of Hic‑5 in several organs (Review).International journal of molecular medicine · 2022Review
- Metabolic reprogram associated with epithelial-mesenchymal transition in tumor progression and metastasis.Genes & diseases · 2020Review
- Cell-specific expression of the transcriptional regulator RHAMM provides a timing mechanism that controls appropriate wound re-epithelialization.The Journal of biological chemistry · 2020Article
- PYK2 promotes HER2-positive breast cancer invasion.Journal of experimental & clinical cancer research : CR · 2019Article
- Role of Pyk2 in Human Cancers.Medical science monitor : international medical journal of experimental and clinical research · 2018Review
- Pyk2 promotes tumor progression in renal cell carcinoma.Oncology letters · 2018Article
- CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling.Molecular cancer · 2016Article
- Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B.Experimental and therapeutic medicine · 2016Article
- Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats.Biochemistry · 2016Article
- Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.Oncotarget · 2015Article
- PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop.Oncotarget · 2015Article
- Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.Clinical and experimental medicine · 2015Article
- Role of focal adhesion kinase in oocyte-follicle communication.Molecular reproduction and development · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsProline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. METHODOLOGY/PRINCIPAL
findingsWe demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization.
conclusionThese data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT.
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