The Interaction between Cancer Stem Cell Marker CD133 and Src Protein Promotes Focal Adhesion Kinase (FAK) Phosphorylation and Cell Migration
The Interaction between Cancer Stem Cell Marker CD133 and Src Protein Promotes Focal Adhesion Kinase (FAK) Phosphorylation and Cell Migration
复制标题
癌症干细胞标志物 CD133 和 Src 蛋白之间的相互作用促进粘着斑激酶 (FAK) 磷酸化和细胞迁移
DOI：
10.1074/jbc.m115.712976
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发表时间：
2016-07-22
影响因子：
4.8
通讯作者：
Jiang, Jianhai
中科院分区：
文献类型：
--
作者：
Liu, Chanjuan;Li, Yinan;Jiang, Jianhai
CD 133是一种广为人知的肿瘤干细胞标志物，已被证明可促进肿瘤转移。然而，CD 133调节转移的机制在很大程度上仍然未知。在这里，我们报告说，CD 133敲低抑制癌细胞迁移，和CD 133过表达促进细胞迁移。CD 133的表达有利于激活Src-粘着斑激酶（FAK）信号通路。进一步的研究表明，CD 133可以与Src相互作用，并且CD 133 C端结构域中845和857氨基酸之间的区域是其与Src相互作用所必需的。这种相互作用激活Src使其底物FAK磷酸化并促进细胞迁移。同样，Src结合缺陷的CD 133突变体失去了增加Src和FAK磷酸化以及促进细胞迁移的能力。已知Src活性抑制剂PP 2抑制Src活性可阻断CD 133诱导的FAK磷酸化活化和细胞迁移。总之，我们的数据表明，通过CD 133和Src之间的相互作用激活FAK促进细胞迁移，为理解CD 133（+）肿瘤细胞的迁移机制提供线索。
CD133, a widely known cancer stem cell marker, has been proved to promote tumor metastasis. However, the mechanism by which CD133 regulates metastasis remains largely unknown. Here, we report that CD133 knockdown inhibits cancer cell migration, and CD133 overexpression promotes cell migration. CD133 expression is beneficial to activate the Src-focal adhesion kinase (FAK) signaling pathway. Further studies show that CD133 could interact with Src, and the region between amino acids 845 and 857 in the CD133 C-terminal domain is indispensable for its interaction with Src. The interaction activates Src to phosphorylate its substrate FAK and to promote cell migration. Likewise, a Src binding-deficient CD133 mutant loses the abilities to increase Src and FAK phosphorylation and to promote cell migration. Inhibition of Src activity by PP2, a known Src activity inhibitor, could block the activation of FAK phosphorylation and cell migration induced by CD133. In summary, our data suggest that activation of FAK by the interaction between CD133 and Src promotes cell migration, providing clues to understand the migratory mechanism of CD133(+) tumor cells.