MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, WC1E 6BT, UK.
J Cell Sci. 2010 Jan 15;123(Pt 2):171-80. doi: 10.1242/jcs.057976. Epub 2009 Dec 21.
At the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial sheet. However, it remains unknown what happens at the boundary between normal and transformed cells. Using Madin-Darby canine kidney (MDCK) cells transformed with temperature-sensitive v-Src, we have examined the interface between normal and Src-transformed epithelial cells. We show that Src-transformed cells are apically extruded when surrounded by normal cells, but not when Src cells alone are cultured, suggesting that apical extrusion occurs in a cell-context-dependent manner. We also observe apical extrusion of Src-transformed cells in the enveloping layer of zebrafish gastrula embryos. When Src-transformed MDCK cells are surrounded by normal MDCK cells, myosin-II and focal adhesion kinase (FAK) are activated in Src cells, which further activate downstream mitogen-activated protein kinase (MAPK). Importantly, activation of these signalling pathways depends on the presence of surrounding normal cells and plays a crucial role in apical extrusion of Src cells. Collectively, these results indicate that interaction with surrounding normal epithelial cells influences the signalling pathways and behaviour of Src-transformed cells.
在癌变的初始阶段，单个上皮细胞中的转化发生。然而，正常细胞和转化细胞之间的边界发生了什么仍然未知。使用温度敏感的 v-Src 转化的 Madin-Darby 犬肾 (MDCK) 细胞，我们检查了正常和 Src 转化上皮细胞之间的界面。我们表明，当周围是正常细胞时，Src 转化细胞被顶部分泌，而当单独培养 Src 细胞时则不会，这表明顶部分泌是一种细胞上下文依赖的方式。我们还观察到在斑马鱼胚层的包被层中 Src 转化的细胞发生顶部分泌。当 Src 转化的 MDCK 细胞被正常的 MDCK 细胞包围时，Src 细胞中的肌球蛋白-II 和粘着斑激酶 (FAK) 被激活，这进一步激活下游丝裂原活化蛋白激酶 (MAPK)。重要的是，这些信号通路的激活依赖于周围正常细胞的存在，并在 Src 细胞的顶部分泌中发挥关键作用。总之，这些结果表明与周围正常上皮细胞的相互作用影响 Src 转化细胞的信号通路和行为。
