Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK

• Published in: FEBS letters 2008-10, Vol.582 (23-24), p.3415-3422
• Main Authors: Zhou, Hong Yan, Wan, Kai Fung, Ip, Carman K.M., Wong, Chris K.C., Mak, Nai Ki, Lo, Kwok Wai, Wong, Alice S.T.
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cell motility; Cell Movement; Enzyme Activation; Hepatocyte growth factor; Hepatocyte Growth Factor - pharmacology; Hepatocyte Growth Factor - physiology; Humans; Invasion; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Matrix Metalloproteinase 9 - metabolism; Met oncogene; Nasopharyngeal cancer; Nasopharyngeal Neoplasms - enzymology; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-met; Receptors, Growth Factor - antagonists & inhibitors; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; RNA, Small Interfering - genetics; Signaling
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2008.09.004

The hepatocyte growth factor (HGF) receptor, Met, is frequently overexpressed in nasopharyngeal cancer (NPC). Here, we showed for the first time that human NPC cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. The downregulation of Met by small interfering RNA decreased tumor cell invasion/migration. HGF significantly increased matrix metalloproteinase-9 production. This was inhibited by blocking phosphatidylinositide 3-kinase (PI3K) and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways. We also demonstrated that PI3K induced activation of JNK, with Akt as a potential point of this cross-talk. These results provide new insights into the molecular mechanism responsible for NPC progression and metastasis.