RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.

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...

Full description

Bibliographic Details
Main Authors: Nithya Subramanian, Saranya Navaneethakrishnan, Jyotirmay Biswas, Rupinder K Kanwar, Jagat R Kanwar, Subramanian Krishnakumar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3737373?pdf=render
_version_ 1819080896170426368
author Nithya Subramanian
Saranya Navaneethakrishnan
Jyotirmay Biswas
Rupinder K Kanwar
Jagat R Kanwar
Subramanian Krishnakumar
author_facet Nithya Subramanian
Saranya Navaneethakrishnan
Jyotirmay Biswas
Rupinder K Kanwar
Jagat R Kanwar
Subramanian Krishnakumar
author_sort Nithya Subramanian
collection DOAJ
description 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.
first_indexed 2024-12-21T19:52:10Z
format Article
id doaj.art-c426ed29c9c24d9e8a9cc4b5dc18c174
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-21T19:52:10Z
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-c426ed29c9c24d9e8a9cc4b5dc18c1742022-12-21T18:52:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7042210.1371/journal.pone.0070422RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.Nithya SubramanianSaranya NavaneethakrishnanJyotirmay BiswasRupinder K KanwarJagat R KanwarSubramanian KrishnakumarT 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.http://europepmc.org/articles/PMC3737373?pdf=render
spellingShingle Nithya Subramanian
Saranya Navaneethakrishnan
Jyotirmay Biswas
Rupinder K Kanwar
Jagat R Kanwar
Subramanian Krishnakumar
RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
PLoS ONE
title RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
title_full RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
title_fullStr RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
title_full_unstemmed RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
title_short RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
title_sort rnai mediated tiam1 gene knockdown inhibits invasion of retinoblastoma
url http://europepmc.org/articles/PMC3737373?pdf=render
work_keys_str_mv AT nithyasubramanian rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma
AT saranyanavaneethakrishnan rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma
AT jyotirmaybiswas rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma
AT rupinderkkanwar rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma
AT jagatrkanwar rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma
AT subramaniankrishnakumar rnaimediatedtiam1geneknockdowninhibitsinvasionofretinoblastoma