Phosphorylation of cMet tyrosine residues in murine ascitic hepatic cancer cell lines with different lymph node metastatic potentials

Li,Ying; Huang,Xiaohua; Zhang,Qiaoshu; Ma,Keli

doi:10.3892/mmr.2013.1527

August 2013 Volume 8 Issue 2

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August 2013 Volume 8 Issue 2

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Article

Phosphorylation of cMet tyrosine residues in murine ascitic hepatic cancer cell lines with different lymph node metastatic potentials

Authors:
- Ying Li
- Xiaohua Huang
- Qiaoshu Zhang
- Keli Ma
View Affiliations / Copyright

Affiliations: Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, P.R. China
Pages: 655-661
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Published online on: June 17, 2013

https://doi.org/10.3892/mmr.2013.1527
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Abstract

The aim of the present study was to determine the molecular mechanism by which the hepatocyte growth factor (HGF) receptor (cMet) regulates lymphatic metastasis in hepatocellular carcinoma. Mouse hepatoma ascites cell lines with different lymph node metastatic potentials, Hca‑F (high metastatic potential) and Hca‑P (low metastatic potential), were cultured in vitro. Cells were treated with HGF, fibronectin (FN) and laminin (LN), and the phosphorylated tyrosine residues of cMet and the activities of intracellular phospholipase Cγ/diacylglycerol/protein kinase C (PLCγ/DAG/PKC) and phosphoinositol‑3‑kinase/protein kinase B (PI3K/AKT) signaling pathways were analyzed comparatively in the two cell lines using western blot analysis and migration assays. Following HGF treatment, the phosphorylation of cMet at Tyr 1313 and 1365 in Hca‑F cells was higher, while the phosphorylation of cMet at Tyr 1349 was lower than that in Hca‑P. The activity of PLCγ/DAG/PKC was increased in Hca‑F cells compared with Hca‑P cells, whereas the activity of PI3K/AKT was reduced. After FN treatment, the phosphorylation of cMet at Tyr 1313 and the activity of the PLCγ/DAG/PKC signaling pathway was increased in Hca‑F cells compared with Hca‑P cells. Following LN treatment, the phosphorylation of cMet at Tyr 1365 and the activity of PLCγ/DAG/PKC was higher in Hca‑F cells than in Hca‑P cells. Results of the current study indicate that a number of ligands stimulate the phosphorylation of cMet at various tyrosine residues, activating different signaling transduction pathways. In addition, the same ligand was observed to phosphorylate different tyrosine residues on cMet in the two cell lines, as well as activate different intracellular signaling transduction pathways. After cMet is activated, various tyrosine residues are phosphorylated, leading to the activation of the PI3K/AKT and PLCγ/DAG/PKC signaling pathways to different extents in the two cells lines. These results may be important in determining the lymph node metastatic potentials of the two cell lines.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Phosphorylation of cMet tyrosine residues in murine ascitic hepatic cancer cell lines with different lymph node metastatic potentials

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Abstract

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