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Tumour-promoting role of SOCS1 in colorectal cancer cells

The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of...

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Autores principales: Tobelaim, William S., Beaurivage, Claudia, Champagne, Audrey, Pomerleau, Véronique, Simoneau, Aline, Chababi, Walid, Yeganeh, Mehdi, Thibault, Philippe, Klinck, Roscoe, Carrier, Julie C., Ferbeyre, Gerardo, Ilangumaran, Subburaj, Saucier, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585755/
https://www.ncbi.nlm.nih.gov/pubmed/26391193
http://dx.doi.org/10.1038/srep14301
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author Tobelaim, William S.
Beaurivage, Claudia
Champagne, Audrey
Pomerleau, Véronique
Simoneau, Aline
Chababi, Walid
Yeganeh, Mehdi
Thibault, Philippe
Klinck, Roscoe
Carrier, Julie C.
Ferbeyre, Gerardo
Ilangumaran, Subburaj
Saucier, Caroline
author_facet Tobelaim, William S.
Beaurivage, Claudia
Champagne, Audrey
Pomerleau, Véronique
Simoneau, Aline
Chababi, Walid
Yeganeh, Mehdi
Thibault, Philippe
Klinck, Roscoe
Carrier, Julie C.
Ferbeyre, Gerardo
Ilangumaran, Subburaj
Saucier, Caroline
author_sort Tobelaim, William S.
collection PubMed
description The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA), and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC.
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spelling pubmed-45857552015-09-29 Tumour-promoting role of SOCS1 in colorectal cancer cells Tobelaim, William S. Beaurivage, Claudia Champagne, Audrey Pomerleau, Véronique Simoneau, Aline Chababi, Walid Yeganeh, Mehdi Thibault, Philippe Klinck, Roscoe Carrier, Julie C. Ferbeyre, Gerardo Ilangumaran, Subburaj Saucier, Caroline Sci Rep Article The SOCS1 (Suppressor Of Cytokine Signalling 1) protein is considered a tumour suppressor. Notably, the SOCS1 gene is frequently silenced in cancer by hypermethylation of its promoter. Besides blocking inflammation, SOCS1 tumour suppressor activity involves Met receptor inhibition and enhancement of p53 tumour suppressor activity. However, the role of SOCS1 in colorectal cancer (CRC) remains understudied and controversial. Here, we investigated SOCS1 relevance for CRC by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas (TCGA), and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. Our results show that SOCS1 mRNA levels in tumours were more often elevated than reduced with respect to matched adjacent normal tissue of CRC specimens (n = 41). The analysis of TCGA dataset of 431 CRC patients revealed no correlation between SOCS1 expression and overall survival. Overexpression of SOCS1 in CRC cells triggered cell growth enhancement, anchorage-independent growth and resistance to death stimuli, whereas knockdown of SOCS1 reduced these oncogenic features. Moreover, SOCS1 overexpression in mouse CT26 cells increased tumourigenesis in vivo. Biochemical analyses showed that SOCS1 pro-oncogenic activity correlated with the down-modulation of STAT1 expression. Collectively, these results suggest that SOCS1 may work as an oncogene in CRC. Nature Publishing Group 2015-09-22 /pmc/articles/PMC4585755/ /pubmed/26391193 http://dx.doi.org/10.1038/srep14301 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tobelaim, William S.
Beaurivage, Claudia
Champagne, Audrey
Pomerleau, Véronique
Simoneau, Aline
Chababi, Walid
Yeganeh, Mehdi
Thibault, Philippe
Klinck, Roscoe
Carrier, Julie C.
Ferbeyre, Gerardo
Ilangumaran, Subburaj
Saucier, Caroline
Tumour-promoting role of SOCS1 in colorectal cancer cells
title Tumour-promoting role of SOCS1 in colorectal cancer cells
title_full Tumour-promoting role of SOCS1 in colorectal cancer cells
title_fullStr Tumour-promoting role of SOCS1 in colorectal cancer cells
title_full_unstemmed Tumour-promoting role of SOCS1 in colorectal cancer cells
title_short Tumour-promoting role of SOCS1 in colorectal cancer cells
title_sort tumour-promoting role of socs1 in colorectal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585755/
https://www.ncbi.nlm.nih.gov/pubmed/26391193
http://dx.doi.org/10.1038/srep14301
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