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...
Main Authors: | , , , , , |
---|---|
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 |