Abi1 gene silencing by short hairpin RNA impairs Bcr-Abl-induced cell adhesion and migration in vitro and leukemogenesis in vivo.
Abi1 gene silencing by short hairpin RNA impairs Bcr-Abl-induced cell adhesion and migration in vitro and leukemogenesis in vivo.
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DOI：
10.1093/carcin/bgn098
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发表时间：
2008-09
期刊：
影响因子：
4.7
通讯作者：
Dai Z
中科院分区：
文献类型：
--
作者：
Yu W;Sun X;Clough N;Cobos E;Tao Y;Dai Z
Abl相互作用子（Abl interactor，Abi）1是Abl酪氨酸激酶的下游靶点，在表达致癌基因Bcr-Abl和v-Abl的白血病细胞中表达异常，虽然越来越多的证据支持Abi 1在肌动蛋白细胞骨架重塑和生长因子/受体信号转导中的作用，但它如何参与Bcr-Abl诱导的白血病发生尚不清楚。我们在这里表明，Abi 1基因沉默短发夹RNA衰减Bcr-Abl诱导的异常肌动蛋白重塑，膜1型金属蛋白酶聚集和抑制细胞粘附和迁移纤连蛋白包被的表面。尽管Abi 1表达的敲低并不影响Bcr-Abl转化的Ba/F3细胞在体外的生长因子非依赖性生长，但它阻碍了这些细胞在非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）小鼠中的竞争性扩增。值得注意的是，Bcr-Abl转化的Ba/F3细胞中Abi 1表达的敲低损害了NOD/SCID小鼠中这些细胞的致白血病潜力。Abi 1部分通过Src家族激酶参与Bcr-Abl诱导的白血病发生，因为Abi 1表达的敲低减弱了Bcr-Abl刺激的林恩活化。总之，这些数据首次提供了支持Abi 1通路在Bcr-Abl诱导的白血病发病机制中的关键作用的直接证据。
Abl interactor (Abi) 1 was first identified as the downstream target of Abl tyrosine kinases and was found to be dysregulated in leukemic cells expressing oncogenic Bcr-Abl and v-Abl. Although the accumulating evidence supports a role of Abi1 in actin cytoskeleton remodeling and growth factor/receptor signaling, it is not clear how it contributes to Bcr-Abl-induced leukemogenesis. We show here that Abi1 gene silencing by short hairpin RNA attenuated the Bcr-Abl-induced abnormal actin remodeling, membrane-type 1 metalloproteinase clustering and inhibited cell adhesion and migration on fibronectin-coated surfaces. Although the knock down of Abi1 expression did not affect growth factor-independent growth of Bcr-Abl-transformed Ba/F3 cells in vitro, it impeded competitive expansion of these cells in non obese diabetic (NOD)/ severe combined immuno-deficiency (SCID) mice. Remarkably, the knock down of Abi1 expression in Bcr-Abl-transformed Ba/F3 cells impaired the leukemogenic potential of these cells in NOD/SCID mice. Abi1 contributes to Bcr-Abl-induced leukemogenesis in part through Src family kinases, as the knock down of Abi1 expression attenuates Bcr-Abl-stimulated activation of Lyn. Together, these data provide for the first time the direct evidence that supports a critical role of Abi1 pathway in the pathogenesis of Bcr-Abl-induced leukemia.
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DOI：
10.1083/jcb.200108035
发表时间：
2002-01-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Innocenti M;Tenca P;Frittoli E;Faretta M;Tocchetti A;Di Fiore PP;Scita G
通讯作者：
Scita G
影响因子：
3.8
作者：
CHEN, WT;LEE, CC;MUELLER, SC
通讯作者：
MUELLER, SC
影响因子：
3.5
作者：
Courtney, KD;Grove, M;Pendergast, AM
通讯作者：
Pendergast, AM
DOI：
10.1083/jcb.200206079
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Innocenti M;Frittoli E;Ponzanelli I;Falck JR;Brachmann SM;Di Fiore PP;Scita G
通讯作者：
Scita G
影响因子：
10.5
作者：
Dai, ZH;Quackenbush, RC;Pendergast, AM
通讯作者：
Pendergast, AM