The splicing factor SRSF6 is amplified and is an oncoprotein inlung and colon cancers
The splicing factor SRSF6 is amplified and is an oncoprotein inlung and colon cancers
复制标题
DOI：
10.1002/path.4129
复制
发表时间：
2013-03-01
影响因子：
7.3
通讯作者：
Karni, Rotem
中科院分区：
文献类型：
--
作者：
Cohen-Eliav, Michal;Golan-Gerstl, Regina;Karni, Rotem
越来越多的证据将选择性剪接过程中的变化与癌症的发展和进展联系起来。然而，剪接因子作为癌症发展驱动因素的直接作用大多是未知的。我们分析了几种剪接因子在结肠癌和肺癌中的基因拷贝数，发现编码剪接因子SRSF6的基因在这些癌症中扩增和过度表达。此外，SRSF6在永生肺上皮细胞中的过表达促进了增殖，保护了它们免受化疗诱导的细胞死亡，并将它们转化为小鼠的肿瘤形成。相反，肺癌和结肠癌细胞系中SRSF6基因的敲除抑制了它们的致瘤能力。SRSF6的上调或下调改变了几个肿瘤抑制基因和癌基因的剪接，以产生致癌亚型并减少肿瘤抑制亚型。我们的数据表明，剪接因子SRSF6是一种癌蛋白，调节肺癌和结肠癌细胞的增殖和生存。
An increasing body of evidence connects alterations in the process of alternative splicing with cancer development and progression. However, a direct role of splicing factors as drivers of cancer development is mostly unknown. We analysed the gene copy number of several splicing factors in colon and lung tumours, and found that the gene encoding for the splicing factor SRSF6 is amplified and over-expressed in these cancers. Moreover, over-expression of SRSF6 in immortal lung epithelial cells enhanced proliferation, protected them from chemotherapy-induced cell death and converted them to be tumourigenic in mice. In contrast, knock-down of SRSF6 in lung and colon cancer cell lines inhibited their tumourigenic abilities. SRSF6 up- or down-regulation altered the splicing of several tumour suppressors and oncogenes to generate the oncogenic isoforms and reduce the tumour-suppressive isoforms. Our data suggest that the splicing factor SRSF6 is an oncoprotein that regulates the proliferation and survival of lung and colon cancer cells.