1 Department of Clinical Medicine - Molekylær Medicinsk afdeling (MOMA), Department of Clinical Medicine, Health, Aarhus University2 unknown3 Department of Clinical Medicine - Molekylær Medicinsk afdeling (MOMA), Department of Clinical Medicine, Health, Aarhus University
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 analyzed the gene copy number of several splicing factors in colon and lung tumors and found that the gene encoding for the splicing factor SRSF6 is amplified and overexpressed in these cancers. Moreover, overexpression of SRSF6 in immortal lung epithelial cells enhanced proliferation, protected them from chemotherapy-induced cell death and converted them to be tumorigenic in mice. In contrast, knockdown of SRSF6 in lung and colon cancer cell lines inhibited their tumorigenic abilities. SRSF6 up- or down regulation altered the splicing of several tumor suppressors and oncogenes to generate the oncogenic isoforms and reduce the tumor suppressive isoforms. Our data suggests that the splicing factor SRSF6 is an oncoprotein which regulates proliferation and survival of lung and colon cancer cells.
Journal of Pathology, 2013, Vol 229, Issue 4, p. 630-639