Abstract | BACKGROUND: METHODS: Expression of Pyk2 was tested by immunohistochemistry in tissue microarrays containing 141 paired HCC samples. Correlation between Pyk2 and vascular endothelial growth factor ( VEGF) expression in clinical samples was analyzed by Spearman rank correlation. Matrigel invasion, anchorage-independent growth assay and immunoblotting were performed to study the effect of Pyk2 on the invasion and progression of HCC cells and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. RESULTS: Higher Pyk2 density in both tumor and peritumor was associated with lower overall survival (P = 0.044; P = 0.041, respectively), serum AFP levels > 1,000 ng/ml (P = 0.013; P = 0.032, respectively) and postoperative distant metastasis (both P < 0.001). However, only higher peritumoral Pyk2 density was related to lower disease-free survival (P = 0.014) and vascular invasion (P = 0.035). A significant correlation between Pyk2 and VEGF density in tumor or peritumoral liver tissue was observed (r = 0. 3133, P = 0.0002; r = 0.5176, P < 0.0001, respectively). Immunoblotting showed that Pyk2 activated PI3K-AKT pathway to upregulate VEGF expression in HL-7702, SMMC-7721 and HepG2 cells. CONCLUSIONS: High Pyk2, especially peritumoral Pyk2 was associated with poor survival, disease recurrence, and metastasis in HCC. PI3K-AKT pathway was involved in Pyk2-mediated VEGF expression during HCC progression and invasion.
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Authors | Jie Cao, Yao Chen, Jing Fu, You-Wen Qian, Yi-Bin Ren, Bo Su, Tao Luo, Rong-Yang Dai, Liang Huang, Jian-Jun Yan, Meng-Chao Wu, Yi-Qun Yan, Hong-Yang Wang |
Journal | Annals of surgical oncology
(Ann Surg Oncol)
Vol. 20 Suppl 3
Pg. S312-23
(Dec 2013)
ISSN: 1534-4681 [Electronic] United States |
PMID | 22618716
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- Phosphatidylinositol 3-Kinase
- Focal Adhesion Kinase 2
- Proto-Oncogene Proteins c-akt
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Topics |
- Apoptosis
- Blotting, Western
- Carcinoma, Hepatocellular
(enzymology, mortality, secondary)
- Cell Adhesion
- Cell Movement
- Cell Proliferation
- Female
- Focal Adhesion Kinase 2
(metabolism)
- Follow-Up Studies
- Gene Expression Regulation, Neoplastic
(physiology)
- Humans
- Immunoenzyme Techniques
- Liver
(metabolism)
- Liver Neoplasms
(enzymology, mortality, pathology)
- Lymphatic Metastasis
- Male
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Staging
- Phosphatidylinositol 3-Kinase
(metabolism)
- Prognosis
- Proto-Oncogene Proteins c-akt
(metabolism)
- RNA, Messenger
(genetics)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Survival Rate
- Tissue Array Analysis
- Tumor Cells, Cultured
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