title: The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Cohen-Eliav
authors.forename: Regina
authors.initials: R
authors.lastname: Golan-Gerstl
authors.forename: Zahava
authors.initials: Z
authors.lastname: Siegfried
authors.forename: Claus L
authors.initials: CL
authors.lastname: Andersen
authors.forename: Kasper
authors.initials: K
authors.lastname: Thorsen
authors.forename: Torben F
authors.initials: TF
authors.lastname: Ørntoft
authors.forename: David
authors.initials: D
authors.lastname: Mu
authors.forename: Rotem
authors.initials: R
authors.lastname: Karni
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D015854:Up-Regulation
chemical_list: D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C489470:SRSF6 protein, human; D000068103:Serine-Arginine Splicing Factors