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The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers
Author(s) -
CohenEliav Michal,
GolanGerstl Regina,
Siegfried Zahava,
Andersen Claus L,
Thorsen Kasper,
Ørntoft Torben F,
Mu David,
Karni Rotem
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4129
Subject(s) - rna splicing , alternative splicing , gene isoform , splicing factor , biology , colorectal cancer , cancer research , lung cancer , gene , tumor suppressor gene , cancer , microbiology and biotechnology , pathology , genetics , carcinogenesis , medicine , rna
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.