c-Myc Overexpression Promotes Osteosarcoma Cell Invasion Via Activation of MEK-ERK Pathway
c-Myc Overexpression Promotes Osteosarcoma Cell Invasion Via Activation of MEK-ERK Pathway
复制标题
DOI：
10.3727/096504012x13522227232237
复制
发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Bi, Wenzhi
中科院分区：
文献类型：
--
作者：
Han, Gang;Wang, Yan;Bi, Wenzhi
骨肉瘤是一种高度转移的恶性肿瘤，通常预后较差。c-Myc扩增与骨肉瘤的发病机制有关。然而，c-myc过表达在骨肉瘤细胞侵袭中的作用仍未被探索。本研究表明，c-myc过表达增强MG-63和SAOS-2骨肉瘤细胞侵袭。MEK抑制剂PD98059或PI3K抑制剂LY294002可降低细胞侵袭，同时下调MMP-2和MMP-9的表达。c-Myc过表达刺激MEK-ERK通路，抑制PI3K-AKT通路的活性。具体而言，PD98509抑制MEK-ERK通路阻断了细胞侵袭增强作用以及MMP-2和MMP-9的表达。本研究表明，c-myc过表达可能通过激活MEK-ERK通路促进骨肉瘤细胞侵袭。
Osteosarcoma is a highly metastatic malignancy often with poor prognosis. c-Myc amplification is implicated in osteosarcoma pathogenesis. However, the role of c-myc overexpression in osteosarcoma cell invasion remains unexplored. This study showed that c-myc overexpression enhanced MG-63 and SAOS-2 osteosarcoma cell invasion. Treatment of MEK inhibitor PD98059 or PI3K inhibitor LY294002 decreased cell invasion along with downregulation of MMP-2 and MMP-9 expression. c-Myc overexpression stimulated MEK-ERK pathway whereas inhibited the activity of PI3K-AKT pathway. Specifically, inhibition of MEK-ERK pathway by PD98509 blocked the enhancement effect on cell invasion as well as MMP-2 and MMP-9 expression. The present study demonstrates that c-myc overexpression promotes osteosarcoma cell invasion, probably via activation of MEK-ERK pathway.