title: Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization.
abstract: Metastatic colonization is an ominous feature of cancer progression. Recent studies have established the importance of pre-mRNA alternative splicing (AS) in cancer biology. However, little is known about the transcriptome-wide landscape of AS associated with metastatic colonization. Both in vitro and in vivo models of metastatic colonization were utilized to study AS regulation associated with cancer metastasis. Transcriptome profiling of prostate cancer cells and derivatives crossing in vitro or in vivo barriers of metastasis revealed splicing factors with significant gene expression changes associated with metastatic colonization. These include splicing factors known to be differentially regulated in epithelial-mesenchymal transition (ESRP1, ESRP2, and RBFOX2), a cellular process critical for cancer metastasis, as well as novel findings (NOVA1 and MBNL3). Finally, RNA-seq indicated a large network of AS events regulated by multiple splicing factors with altered gene expression or protein activity. These AS events are enriched for pathways important for cell motility and signaling, and affect key regulators of the invasive phenotype such as CD44 and GRHL1.
  
  
  CONCLUSIONS
  Transcriptome-wide remodeling of AS is an integral regulatory process underlying metastatic colonization, and AS events affect the metastatic behavior of cancer cells.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
authors.forename: Zhi-xiang
authors.initials: ZX
authors.lastname: Lu
authors.affiliation: Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. Department of Pathology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
authors.forename: Juw Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
authors.forename: Shihao
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Tokheim
authors.affiliation: Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. Department of Pathology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa. yxing@ucla.edu Michael-henry@uiowa.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California. yxing@ucla.edu Michael-henry@uiowa.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xing
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger