Gene Set: LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_UP

Standard name LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_UP
Systematic name M515
Brief description Up-regulated genes displaying alternative splicing in MDA-MB-435 cells (breast cancer) whose metastatic potential has been reduced by expression of NME1 [GeneID=4830].
Full description or abstract The role of Gemin5 in alternative mRNA splicing, tumor cell motility, and proteomic instability was investigated. Isotope Capture Affinity Tag proteomic analysis was conducted on MDA-MB-435 tumor cells transfected with either a control vector (C-100) or the Nm23-H1 metastasis suppressor (H1-177). Ingenuity pathway analysis revealed that RNA posttranscriptional processing was the most prominent class of differentially expressed proteins. Within this category, overexpression of Acinus1, Poly(a) binding protein, HNRPA2B1, Bop1, and Gemin5 was confirmed in less metastatic H1-177 cells. Overexpression of the latter four proteins was also observed in the lower metastatic antisense Ezrin transfectant of a murine osteosarcoma model system, confirming the general relevance of the trends. Gemin5, a component of the spliceosomal complex, was chosen for further study. Analysis of global mRNA splicing by SpliceArray chips revealed that 16 genes were differentially spliced in C-100 compared with H1-177 cells; transient transfection of gemin5 into C-100 cells restored the splice pattern to that of H1-177 cells. Alternative splicing patterns for the engulfment and cell motility 1 and thrombospondin 4 genes were confirmed by semiquantitative reverse transcription-PCR. Gemin5 overexpression coordinately reduced C-100 cell motility by 50%, and siRNA-mediated reduction of Gemin5 expression increased the motility of H1-177 cells by 2-fold (P < 0.004). The data provide the first demonstration that alterations in the expression of a spliceosome protein can effect both specific splicing events and tumor cell motility. The data also show that changes in mRNA splicing patterns accompany metastatic progression, which may contribute to proteome instability.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18245461   Authors: Lee JH,Horak CE,Khanna C,Meng Z,Yu LR,Veenstra TD,Steeg PS
Exact source Table 3.1S, 3.2S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform Human_RefSeq
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Version history 3.0: First introduced

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