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GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring

GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by Interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motilit...

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Autores principales: Sun, Peng, Nallar, Shreeram C., Kalakonda, Sudhakar, Lindner, Daniel J., Martin, Stuart S., Kalvakolanu, Dhananjaya V.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662763/
https://www.ncbi.nlm.nih.gov/pubmed/19151760
http://dx.doi.org/10.1038/onc.2008.480
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author Sun, Peng
Nallar, Shreeram C.
Kalakonda, Sudhakar
Lindner, Daniel J.
Martin, Stuart S.
Kalvakolanu, Dhananjaya V.
author_facet Sun, Peng
Nallar, Shreeram C.
Kalakonda, Sudhakar
Lindner, Daniel J.
Martin, Stuart S.
Kalvakolanu, Dhananjaya V.
author_sort Sun, Peng
collection PubMed
description GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by Interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motility by cytoskeletal remodeling especially the formation of podosomes and. Here we show that GRIM-19 inhibited the v-Src-induced cell motility by inhibiting cytoskeletal remodeling i.e., podosome formation. We also show that the N-terminus of GRIM-19 played a major role in this process and identified critical residues in this region. More importantly, we show that tumor-associated GRIM-19 mutations disrupted its ability to inhibit v-Src-induced cell motility. These actions appear to occur independently of STAT3, a known target of GRIM-19-mediated inhibition. Lastly, tumor-associated GRIM-19 mutants significantly lost their ability to control v-Src-induced metastases in vivo, indicating the biological and pathological significance of these observations.
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spelling pubmed-26627632009-09-12 GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring Sun, Peng Nallar, Shreeram C. Kalakonda, Sudhakar Lindner, Daniel J. Martin, Stuart S. Kalvakolanu, Dhananjaya V. Oncogene Article GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by Interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motility by cytoskeletal remodeling especially the formation of podosomes and. Here we show that GRIM-19 inhibited the v-Src-induced cell motility by inhibiting cytoskeletal remodeling i.e., podosome formation. We also show that the N-terminus of GRIM-19 played a major role in this process and identified critical residues in this region. More importantly, we show that tumor-associated GRIM-19 mutations disrupted its ability to inhibit v-Src-induced cell motility. These actions appear to occur independently of STAT3, a known target of GRIM-19-mediated inhibition. Lastly, tumor-associated GRIM-19 mutants significantly lost their ability to control v-Src-induced metastases in vivo, indicating the biological and pathological significance of these observations. 2009-01-19 2009-03-12 /pmc/articles/PMC2662763/ /pubmed/19151760 http://dx.doi.org/10.1038/onc.2008.480 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Sun, Peng
Nallar, Shreeram C.
Kalakonda, Sudhakar
Lindner, Daniel J.
Martin, Stuart S.
Kalvakolanu, Dhananjaya V.
GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title_full GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title_fullStr GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title_full_unstemmed GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title_short GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
title_sort grim-19 inhibits v-src-induced cell motility by interfering with cytoskeletal restructuring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662763/
https://www.ncbi.nlm.nih.gov/pubmed/19151760
http://dx.doi.org/10.1038/onc.2008.480
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