Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK.
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.
Zhou
Hong Yan
HY
School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong.
Wan
Kai Fung
KF
Ip
Carman K M
CK
Wong
Chris K C
CK
Mak
Nai Ki
NK
Lo
Kwok Wai
KW
Wong
Alice S T
AS
D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D034741:RNA, Small Interfering / Q000235:genetics; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D017228:Hepatocyte Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; C491743:MET protein, human