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Hepatocyte growth factor enhances proteolysis and invasiveness of human nasopharyngeal cancer cells through activation of PI3K and JNK
Author(s) -
Zhou Hong Yan,
Wan Kai Fung,
Ip Carman K.M.,
Wong Chris K.C.,
Mak Nai Ki,
Lo Kwok Wai,
Wong Alice S.T.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.09.004
Subject(s) - hepatocyte growth factor , pi3k/akt/mtor pathway , protein kinase b , kinase , microbiology and biotechnology , cancer research , signal transduction , protein kinase r , protein kinase a , motility , biology , growth factor , chemistry , p38 mitogen activated protein kinases , mitogen activated protein kinase kinase , receptor , biochemistry
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.