科研之友
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摘要
Fibronectin (FN) has been recognized as the key element in promoting cell adhesion, migration and oncogenic transformation. alpha v beta 6 integrin binds with FN in an RGD-dependent manner and is associated with invasion and poor prognosis in many types of cancers. The extracellular matrix (ECM) is commonly degraded and becomes disorganized in cancers. Previous studies have shown that FN can be degraded into fragments by MMP-9 in vitro; MMP-9 expression is upregulated in breast cancer, therefore, the role of degraded FN in breast cancer progression needs to be investigated. In the present study, expression of beta 6 integrin in breast cancer tissues was analyzed. The data were quite consistent with the hypothesis that beta 6 integrin expression is an indicator of poor prognosis. Cell surface expression of beta 6 integrin was correlated with the invasive behavior of the breast cancer cell lines. MMP-9-degraded FN was used to explore its effects on cell invasion and expression of beta 6 integrin. The results indicated that MMP-9-degraded FN can adjust constituents of the alpha v beta 6 heterodimers at the early phase and significantly elevate amounts of beta 6 integrin subunits at a later period. To better elucidate the mechanism by which beta 6 integrin regulates FN-induced cell migration and invasion, we determined the expression and activity of the downstream kinases of beta 6 integrin, and elucidated that focal adhesion kinase (FAK)-Src interaction promoted the invasion and migration of breast cancer cells after treatment of MMP-9-degraded FN through the Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways.
- 出版日期2015-9
- 单位潍坊医学院
