M-RIP, a novel target of JNK signaling and a requirement for human cancer cell invasion.
Cell motility is involved in physiological and pathological processes such as the invasion and migration of cells. c-Jun N-terminal kinase (JNK) cascades are involved in the invasion and metastasis of cancer cells. However, little is known about the downstream signaling of JNK. In the present study, we used small interfering RNA (siRNA) directed against JNK1 to reduce its expression. We used microarray techniques to compare the gene expression profiles of epidermal growth factor (EGF)-stimulated HeLa cells with and without JNK1 siRNA treatment. We identified a JNK1 target gene, myosin phosphatase-Rho interacting protein (M-RIP). RNA interference-mediated inhibition of JNK1 strongly inhibited M-RIP mRNA expression induced by EGF, as well as the invasion of HeLa cells. In addition, M-RIP siRNA-treated cells showed significantly reduced invasive activity. Thus, a functional analysis of JNK1 and M-RIP with RNA interference reveals a critical role for this cascade in the invasive behavior of cancer cells.
Ono
Ryoko
R
Department of Gastroenterological Surgery, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Matsuoka
Junji
J
Yamatsuji
Tomoki
T
Naomoto
Yoshio
Y
Tanaka
Noriaki
N
Matsui
Hideki
H
Matsushita
Masayuki
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D039561:Eukaryotic Initiation Factor-4E; C498552:MPRIP protein, human; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048055:Mitogen-Activated Protein Kinase 8