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首页> 外文OA文献 >The Protrusive Phase and Full Development of Integrin-Dependent Adhesions in Colon Epithelial Cells Require FAK- and ERK-Mediated Actin Spike Formation: Deregulation in Cancer Cells1
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The Protrusive Phase and Full Development of Integrin-Dependent Adhesions in Colon Epithelial Cells Require FAK- and ERK-Mediated Actin Spike Formation: Deregulation in Cancer Cells1

机译：结肠上皮细胞中整合素依赖性黏附的突出期和充分发育需要FAK和ERK介导的肌动蛋白突突形成：癌细胞中的放松调节1

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Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on αvβ6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both αvβ6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK). Furthermore, phosphorylated ERK was targeted to newly forming cell-matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK-tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK-ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK-ERK-dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression.
机译：整联蛋白通过影响细胞应答和基质依赖性粘附在肿瘤进展中起重要作用。然而，对上皮细胞中基质依赖性粘附装配的调控了解甚少。我们已经研究了在纤连蛋白上铺板后结肠癌细胞中细胞基质粘附组装的整合素和信号传导要求。在这些以及它们所衍生的腺瘤细胞中的粘附装配在很大程度上取决于αvβ6整联蛋白，并且需要酪氨酸-397在FAK上进行磷酸化。在腺瘤向癌的转移过程中，纤连蛋白诱导的粘附装配的速率以及αvβ6整合素和FAK的表达均增加。依赖于基质的粘附组装过程，尤其是最佳的细胞扩散所需的复杂突起的最后阶段，需要细胞外信号调节激酶（ERK）的活性。此外，磷酸化的ERK靶向于癌细胞中新形成的细胞-基质粘附，而不是腺瘤细胞，并且抑制FAK-酪氨酸397磷酸化或MEK抑制了周围部位磷酸化ERK的出现。此外，对MEK-ERK激活的抑制作用阻止了外周肌动蛋白微峰的形成，这对于细胞-基质粘附组装的突出阶段是必需的。因此，MEK-ERK依赖的周边肌动蛋白重组是完整的整联蛋白诱导的粘附的发展所必需的，并且该途径在结肠癌进展的体外模型中得到刺激。

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