Boudria Rofia, Laurienté Vanessa, Oudar Antonin, Harouna-Rachidi Souleymane, Dondi Elisabetta, Le Roy Christine, Gardano Laura, Varin-Blank Nadine, Guittat Lionel
INSERM, UMR 978, Bobigny, France; Labex Inflamex, Université Sorbonne Paris Nord, UFR SMBH, Bobigny, France.
INSERM, UMR 978, Bobigny, France; Labex Inflamex, Université Sorbonne Paris Nord, UFR SMBH, Bobigny, France.
Cell Signal. 2021 Oct;86:110079. doi: 10.1016/j.cellsig.2021.110079. Epub 2021 Jul 9.
Vav1 exhibits two signal transducing properties as an adaptor protein and a regulator of cytoskeleton organization through its Guanine nucleotide Exchange Factor module. Although the expression of Vav1 is restricted to the hematopoietic lineage, its ectopic expression has been unraveled in a number of solid tumors. In this study, we show that in lung cancer cells, as such in hematopoietic cells, Vav1 interacts with the Spleen Tyrosine Kinase, Syk. Likewise, Syk interacts with β-catenin and, together with Vav1, regulates the phosphorylation status of β-catenin. Depletion of Vav1, Syk or β-catenin inhibits Rac1 activity and decreases cell migration suggesting the interplay of the three effectors to a common signaling pathway. This model is further supported by the finding that in turn, β-catenin regulates the transcription of Syk gene expression. This study highlights the elaborated connection between Vav1, Syk and β-catenin and the contribution of the trio to cell migration.
Vav1作为一种衔接蛋白，通过其鸟嘌呤核苷酸交换因子模块展现出两种信号转导特性，即作为细胞骨架组织的调节剂。尽管Vav1的表达仅限于造血谱系，但其异位表达已在多种实体瘤中被发现。在本研究中，我们表明在肺癌细胞中，就像在造血细胞中一样，Vav1与脾酪氨酸激酶Syk相互作用。同样，Syk与β-连环蛋白相互作用，并与Vav1一起调节β-连环蛋白的磷酸化状态。Vav1、Syk或β-连环蛋白的缺失会抑制Rac1活性并降低细胞迁移，这表明这三种效应器在共同信号通路中相互作用。β-连环蛋白反过来调节Syk基因表达的发现进一步支持了该模型。这项研究突出了Vav1、Syk和β-连环蛋白之间的精细联系以及三者对细胞迁移的作用。
