RRC ID 44588
著者 Subramanian N, Navaneethakrishnan S, Biswas J, Kanwar RK, Kanwar JR, Krishnakumar S.
タイトル RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
ジャーナル PLoS One
Abstract T lymphoma invasion and metastasis protein (Tiam1) is up-regulated in variety of cancers and its expression level is related to metastatic potential of the type of cancer. Earlier, Tiam1 was shown to be overexpressed in retinoblastoma (RB) and we hypothesized that it was involved in invasiveness of RB. This was tested by silencing Tiam1 in RB cell lines (Y79 and Weri-Rb1) using siRNA pool, targeting different regions of Tiam1 mRNA. The cDNA microarray of Tiam1 silenced cells showed gene regulations altered by Tiam1 were predominantly on the actin cytoskeleton interacting proteins, apoptotic initiators and tumorogenic potential targets. The silenced phenotype resulted in decreased growth and increased apoptosis with non-invasive characteristics. Transfection of full length and N-terminal truncated construct (C1199) clearly revealed membrane localization of Tiam1 and not in the case of C580 construct. F-actin staining showed the interaction of Tiam1 with actin in the membrane edges that leads to ruffling, and also imparts varying invasive potential to the cell. The results obtained from our study show for the first time that Tiam1 modulates the cell invasion, mediated by actin cytoskeleton remodeling in RB.
巻・号 8(8)
ページ e70422
公開日 2013-1-1
DOI 10.1371/journal.pone.0070422
PII PONE-D-13-09469
PMID 23950931
PMC PMC3737373
MeSH Actin Cytoskeleton / metabolism Actins / genetics Actins / metabolism Apoptosis / genetics Blotting, Western Cell Line, Tumor Cell Membrane / metabolism Cell Movement / genetics* Cell Proliferation Gene Expression Regulation, Neoplastic Guanine Nucleotide Exchange Factors / genetics* Guanine Nucleotide Exchange Factors / metabolism Humans Microscopy, Fluorescence Mutation Neoplasm Invasiveness Oligonucleotide Array Sequence Analysis Protein Binding RNA Interference* Retinoblastoma / genetics* Retinoblastoma / metabolism Retinoblastoma / pathology Reverse Transcriptase Polymerase Chain Reaction T-Lymphoma Invasion and Metastasis-inducing Protein 1 Transcriptome
IF 2.74
引用数 22
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Y79(RCB1645) WERI-Rb-1(RCB2146)