Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration.

Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration.
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DOI:
10.1002/mc.23410
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发表时间:
2022-07
影响因子:
4.6
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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Src酪氨酸激酶是一种强肿瘤促进剂。经过世纪的研究,已经阐明了驱动其致癌潜力的基本机制。Src磷酸化效应蛋白促进肿瘤进展的标志。例如,Src与Cas粘着斑衔接蛋白结合以促进锚定非依赖性细胞生长。此外,Src磷酸化Cas以诱导Pdpn表达,从而促进细胞迁移。Pdpn是一种跨膜受体,在没有致癌Src激酶活性的情况下可以独立地增加细胞迁移。然而,据我们所知,在没有Pdpn表达的情况下,Src激酶活性对锚定非依赖性细胞生长和迁移的影响尚未被研究。在这里,我们分析了诱导型Src激酶构建体在有和没有外源性Pdpn表达的敲除细胞中对细胞形态迁移和锚定非依赖性生长的影响。我们报告说,Src促进锚定独立的细胞生长的情况下,Pdpn的表达。相反,Src不能促进细胞迁移的情况下,Pdpn的表达。此外,持续的Src激酶活性是细胞呈现转化形态所必需的,因为细胞在Src激酶活性停止后恢复到非转化形态。我们还使用磷酸化蛋白质组学分析,以确定28蛋白磷酸化的Src转化细胞中的Pdpn依赖的方式。总之,这些数据表明,Src利用Pdpn促进转化细胞的生长和运动的互补,但平行,而不是串行,途径。
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 in order 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.
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