Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway
| Autor: | Zhi-Gang Zheng, Zhaoxu Yang, Haimin Li, Jingshi Zhou, Wenjie Song, Kaishan Tao, Xiao-lei Li, Kefeng Dou, Qing-jun Li, Nan You, Xing Wang, Liang Zhou |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Oncology Cancer Research medicine.medical_specialty Carcinoma Hepatocellular Biology Metastasis chemistry.chemical_compound Internal medicine medicine Carcinoma Humans Tensin PTEN Neoplasm Invasiveness Neoplasm Metastasis Mitogen-Activated Protein Kinase 7 PI3K/AKT/mTOR pathway Aged Neoplasm Staging Oncogene Liver Neoplasms PTEN Phosphohydrolase Hep G2 Cells Middle Aged Cell cycle Prognosis medicine.disease digestive system diseases Elafin Gene Expression Regulation Neoplastic Vascular endothelial growth factor Matrix Metalloproteinase 9 chemistry Cancer research biology.protein Matrix Metalloproteinase 2 Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | International Journal of Oncology. 43:793-802 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2013.1992 |
| Popis: | Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and it carries a poor prognosis due to a high rate of recurrence or metastasis after surgery. Bmi-1 plays a significant role in the growth and metastasis of many solid tumours. However, the exact mechanisms underlying Bmi-1-mediated cell invasion and metastasis, especially in HCC, are not yet known. In the present study, we sought to evaluate the expression of Bmi-1 in HCC samples and its relationship with clinicopathological characteristics and prognostic value, we also investigated related mechanisms underlying Bmi-1-mediated cell invasion in HCC. Our results showed that Bmi-1 is upregulated in HCC tissues compared to matched non-cancer liver tissues; and its expression is positively associated with tumour size, metastasis, venous invasion and AJCC TNM stage, respectively; multivariate analysis showed that high expression of Bmi-1 was an independent prognostic factor for overall survival. In addition, the shRNA-mediated inhibition of Bmi-1 reduced the invasiveness of two HCC cell lines in vitro by upregulating phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) expression, inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and downregulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 and vascular endothelial growth factor (VEGF). These data demonstrate that Bmi-1 plays a vital role in HCC invasion and that Bmi-1 is a potential therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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