Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing, China.
Cancer Lett. 2013 Apr 28;330(2):208-16. doi: 10.1016/j.canlet.2012.11.043. Epub 2012 Dec 2.
Kindlin-2, as a focal adhesion protein, has been found to regulate tumor progression. However, the mechanism underlying Kindlin-2 regulation of tumor progression is largely unknown. Here, we report that Kindlin-2 regulates breast cancer cell proliferation, apoptosis and chromosomal abnormalities in both gain and loss of function assays. Functionally, overexpression of Kindlin-2 promotes tumor formation in implanted xenograft while knockdown of Kindlin-2 inhibits tumor growth in mice. Mechanistically, an array-based comparative genomic hybridization and karyotype analyses indicate that ectopic expression of Kindlin-2 leads to genome instability in breast cancer cells. Our data suggest a novel mechanism that Kindlin-2 regulates breast cancer progression by inducing genome instability.
Kindlin-2 作为黏着斑蛋白，已被发现可调节肿瘤进展。然而，Kindlin-2 调节肿瘤进展的机制在很大程度上尚不清楚。在这里，我们报告 Kindlin-2 通过功能获得和功能丧失实验调节乳腺癌细胞增殖、凋亡和染色体异常。功能上，Kindlin-2 的过表达促进了植入性异种移植物中的肿瘤形成，而 Kindlin-2 的敲低则抑制了小鼠中的肿瘤生长。从机制上讲，基于阵列的比较基因组杂交和核型分析表明，Kindlin-2 的异位表达导致乳腺癌细胞的基因组不稳定。我们的数据表明了一种新的机制，即 Kindlin-2 通过诱导基因组不稳定性来调节乳腺癌的进展。
