The Src tyrosine kinase is a strong tumor promotor. Over a century of research has elucidated fundamental mechanisms that drive its oncogenic potential. Src phosphorylates effector proteins to promote hallmarks of tumor progression. For example, Src associates with the Cas focal adhesion adaptor protein to promote anchorage independent cell growth. In addition, Src phosphorylates Cas to induce Pdpn expression to promote cell migration. Pdpn is a transmembrane receptor that can independently increase cell migration in the absence of oncogenic Src kinase activity. However, to our knowledge, effects of Src kinase activity on anchorage independent cell growth and migration have not been examined in the absence of Pdpn expression. Here, we analyzed the effects of an inducible Src kinase construct in knockout cells with and without exogenous Pdpn expression on cell morphology migration and anchorage independent growth. We report that Src promoted anchorage independent cell growth in the absence of Pdpn expression. In contrast, Src was not able to promote cell migration in the absence of Pdpn expression. In addition, continued Src kinase activity was required for cells to assume a transformed morphology since cells reverted to a nontransformed morphology upon cessation of Src kinase activity. We also used phosphoproteomic analysis to identify 28 proteins that are phosphorylated in Src transformed cells in a Pdpn dependent manner. Taken together, these data indicate that Src utilizes Pdpn to promote transformed cell growth and motility in complementary, but parallel, as opposed to serial, pathways.

中文翻译：

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Src 激酶和足足蛋白对贴壁非依赖性细胞生长和迁移的独立影响

Src 酪氨酸激酶是一种强肿瘤促进剂。一个多世纪的研究已经阐明了驱动其致癌潜力的基本机制。Src 磷酸化效应蛋白以促进肿瘤进展的标志。例如，Src 与 Cas 粘着斑接头蛋白结合以促进不依赖贴壁的细胞生长。此外，Src 磷酸化 Cas 诱导 Pdpn 表达，促进细胞迁移。Pdpn 是一种跨膜受体，在缺乏致癌 Src 激酶活性的情况下可以独立增加细胞迁移。然而，据我们所知，在 Pdpn 表达缺失的情况下，Src 激酶活性对贴壁独立细胞生长和迁移的影响尚未得到检验。这里，我们分析了在有或没有外源 Pdpn 表达的敲除细胞中诱导型 Src 激酶构建体对细胞形态迁移和贴壁独立生长的影响。我们报告说，在 Pdpn 表达缺失的情况下，Src 促进了贴壁独立的细胞生长。相反，在缺乏 Pdpn 表达的情况下，Src 不能促进细胞迁移。此外，细胞需要持续的Src激酶活性才能呈现转化的形态，因为Src激酶活性停止后细胞会恢复到非转化的形态。我们还使用磷酸蛋白质组学分析来鉴定在 Src 转化细胞中以 Pdpn 依赖性方式磷酸化的 28 种蛋白质。综上所述，这些数据表明 Src 利用 Pdpn 以互补但平行的方式促进转化细胞的生长和运动，