The emerging role of splicing factors in cancer

被引:142
作者
Grosso, Ana Rita [1 ]
Martins, Sandra [1 ]
Carmo-Fonseca, Maria [1 ]
机构
[1] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal
关键词
cancer; pre-mRNA splicing; spliceosome; splicing factor; therapeutic target;
D O I
10.1038/embor.2008.189
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent progress in global sequence and microarray data analysis has revealed the increasing complexity of the human transcriptome. Alternative splicing generates a huge diversity of transcript variants and disruption of splicing regulatory networks is emerging as an important contributor to various diseases, including cancer. Current efforts to establish the dynamic repertoire of transcripts that are generated in health and disease are showing that many cancer-associated alternative-splicing events occur in the absence of mutations in the affected genes. A growing body of evidence reveals changes in splicing-factor expression that correlate with cancer development, progression and response to therapy. Here, we discuss how recent links between cancer and altered expression of proteins implicated in splicing regulation are bringing the splicing machinery to the fore as a potential target for anticancer treatment.
引用
收藏
页码:1087 / 1093
页数:7
相关论文
共 53 条
[11]   U2AF-homology motif interactions are required for alternative splicing regulation by SPF45 [J].
Corsini, Lorenzo ;
Bonnal, Sophie ;
Basquin, Jerome ;
Hothorn, Michael ;
Scheffzek, Klaus ;
Valcarcel, Juan ;
Sattler, Michael .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (07) :620-U2
[12]   Strategies for optimizing combinations of molecularly targeted anticancer agents [J].
Dancey, Janet E. ;
Chen, Helen X. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (08) :649-659
[13]   Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma [J].
Denkert, C ;
Weichert, W ;
Winzer, KJ ;
Müller, BM ;
Noske, A ;
Niesporek, S ;
Kristiansen, G ;
Guski, H ;
Dietel, M ;
Hauptmann, S .
CLINICAL CANCER RESEARCH, 2004, 10 (16) :5580-5586
[14]  
Ding WQ, 2002, CANCER RES, V62, P947
[15]  
Fischer DC, 2004, ONCOL REP, V11, P1085
[16]   Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene [J].
Ghigna, C ;
Giordano, S ;
Shen, HH ;
Benvenuto, F ;
Castiglioni, F ;
Comoglio, PM ;
Green, MR ;
Riva, S ;
Biamonti, G .
MOLECULAR CELL, 2005, 20 (06) :881-890
[17]   Soluble CD44 isoforms in serum as potential markers of metastatic gastric carcinoma [J].
Harn, HJ ;
Ho, LI ;
Shyu, RY ;
Yuan, JS ;
Lin, FG ;
Young, TH ;
Liu, CA ;
Tang, HS ;
Lee, WH .
JOURNAL OF CLINICAL GASTROENTEROLOGY, 1996, 22 (02) :107-110
[18]   Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma [J].
Hayes, GM ;
Carrigan, PE ;
Beck, AM ;
Miller, LJ .
CANCER RESEARCH, 2006, 66 (07) :3819-3827
[19]   Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas [J].
Hayes, Gregory M. ;
Carrigan, Patricia E. ;
Miller, Laurence J. .
CANCER RESEARCH, 2007, 67 (05) :2072-2080
[20]   Alternative splicing of the multidrug resistance protein 1/ATP binding cassette transporter subfamily gene in ovarian cancer creates functional splice variants and is associated with increased expression of the splicing factors PTB and SRp20 [J].
He, XL ;
Ee, PLR ;
Coon, JS ;
Beck, WT .
CLINICAL CANCER RESEARCH, 2004, 10 (14) :4652-4660