【摘 要】
：
Focal adhesion kinase (FAK) is overexpressed in a variety of cancers such as breast, colon, prostate, ovary and lung.However, the mechanism by which extracellular matrix fibronectin stimulates lung ca
【机 构】
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Laboratory of Medical Genetics, Harbin Medical University, Harbin 150086, China
【出 处】
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第八次全国医学遗传学学术会议(中华医学会2009年医学遗传学年会)
论文部分内容阅读
Focal adhesion kinase (FAK) is overexpressed in a variety of cancers such as breast, colon, prostate, ovary and lung.However, the mechanism by which extracellular matrix fibronectin stimulates lung cancer cell migration and invasion via FAK remains to be investigated.In the present study, we examined the FAK signaling pathways in relation to calpain-2 and RhoA in fibronectin-me diated lung cancer cell migration and invasion.We found that A549 lung epithelial cells stimulated by fibronectin showed increased phosphorylation of FAK and its downstream targets, Src, ERK1/2, PI3K, and Akt.Consistent with this observation, depletion of FAK by siRNA resulted in inhibition of Src, ERK1/2, PI3K, and Akt activity.In addition, the Src inhibitor, PP2, blocked the phosphoryl ation of FAK, ERK1/2, PI3K, and Akt.Conversely, inhibition of MEK1/2 using PD98059 reduced the expression of MMP9 and cal pain-2.The PI3K inhibitor, LY294002, further blocked the expression of MMP9 and RhoA.Inhibition of both MEK1/2 and PI3K caused reduced cell migration and invasion.Together, our data suggest that fibronectin-mediated activation of FAK that leads to lung cancer metastasis could occur through ERK or PI3K/Akt regulation of MMP9/calpain-2 or MMP9/RhoA activity, respectively.
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