M-RIP, a novel target of JNK signaling and a requirement for human cancer cell invasion
M-RIP, a novel target of JNK signaling and a requirement for human cancer cell invasion
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DOI：
10.3892/ijmm_00000009
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发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Matsushita, Masayuki
中科院分区：
文献类型：
--
作者：
Ono, Ryoko;Matsuoka, Junji;Matsushita, Masayuki
细胞运动参与细胞的侵袭和迁移等生理和病理过程。c-Jun n -末端激酶（JNK）级联参与了癌细胞的侵袭和转移。然而，对JNK的下游信号传导知之甚少。在本研究中，我们使用小干扰RNA （siRNA）靶向JNK1以降低其表达。我们使用微阵列技术比较了表皮生长因子（EGF）刺激的HeLa细胞在JNK1 siRNA处理和未处理的情况下的基因表达谱。我们确定了JNK1的靶基因，肌球蛋白磷酸酶- rho相互作用蛋白（M-RIP）。RNA干扰介导的JNK1抑制强烈抑制EGF诱导的M-RIP mRNA表达，以及对HeLa细胞的侵袭。此外，M-RIP sirna处理的细胞表现出显著降低的侵袭活性。因此，JNK1和M-RIP在RNA干扰下的功能分析揭示了该级联在癌细胞侵袭行为中的关键作用。
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.