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Abstract：
The reorganization of the cell cytoskeleton and changes in the content of cell adhesion molecules are crucial during the metastatic spread of tumor cells. Colorectal cancer (CRC) cells express high SMAD7, a protein involved in the control of CRC cell growth. In the present study, we evaluated whether SMAD7 regulates the cytoskeleton reorganization and dynamics in CRC. Knockdown of SMAD7 with a specific antisense oligonucleotide (AS) in HCT116 and DLD1, two human CRC cell lines, reduced the migration rate and the content of F-ACTIN filaments. A gene array, real-time PCR, and Western blotting of SMAD7 AS-treated cells showed a marked down-regulation of the X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis family, which has been implicated in cancer cell migration. IL-6 and IL-22, two cytokines that activate STAT3, enhanced XIAP in cancer cells, and such induction was attenuated in SMAD7-deficient cells. Finally, in human CRC, SMAD7 mRNA correlated with XIAP expression. Our data show that SMAD7 positively regulates XIAP expression and migration of CRC cells, and suggest a mechanism by which SMAD7 controls the architecture components of the CRC cell cytoskeleton.
摘要：
在肿瘤细胞的转移扩散过程中，细胞骨架的重组和细胞粘附分子含量的变化至关重要。结直肠癌（CRC）细胞表达高SMAD7，这是一种与CRC细胞生长控制有关的蛋白质。在本研究中,我们评估了SMAD7是否调节CRC中的细胞骨架重组和动力学。用特异性反义寡核苷酸（AS）在两种人类CRC细胞系HCT116和DLD1中敲除SMAD7，降低了迁移速率和F-肌动蛋白丝的含量。一个基因阵列,实时PCR，SMAD7AS处理细胞的Western印迹显示X连锁凋亡抑制蛋白（XIAP）明显下调，凋亡抑制剂家族的成员，这与癌细胞迁移有关。IL-6和IL-22，两种激活STAT3的细胞因子，增强癌细胞中的XIAP，并且这种诱导在SMAD7缺陷细胞中减弱。最后,在人类CRC中，SMAD7mRNA与XIAP表达相关。我们的数据显示SMAD7正调控XIAP表达和CRC细胞的迁移,并提出了SMAD7控制CRC细胞骨架结构成分的机制。
