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) |