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SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma
Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by SNAI2 gene) and SOX9, that are associated with advanced stage lung cancers and are implicated in the...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801727/ https://www.ncbi.nlm.nih.gov/pubmed/26387547 http://dx.doi.org/10.1038/onc.2015.351 |
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author | Luanpitpong, Sudjit Li, Jingting Manke, Amruta Brundage, Kathleen Ellis, Emily McLaughlin, Sarah L. Angsutararux, Paweorn Chanthra, Nawin Voronkova, Maria Chen, Yi Charlie Wang, Liying Chanvorachote, Pithi Pei, Ming Issaragrisil, Surapol Rojanasakul, Yon |
author_facet | Luanpitpong, Sudjit Li, Jingting Manke, Amruta Brundage, Kathleen Ellis, Emily McLaughlin, Sarah L. Angsutararux, Paweorn Chanthra, Nawin Voronkova, Maria Chen, Yi Charlie Wang, Liying Chanvorachote, Pithi Pei, Ming Issaragrisil, Surapol Rojanasakul, Yon |
author_sort | Luanpitpong, Sudjit |
collection | PubMed |
description | Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by SNAI2 gene) and SOX9, that are associated with advanced stage lung cancers and are implicated in the regulation of CSCs. Inhibition of either SLUG or SOX9 sufficiently inhibits CSCs in human lung cancer cells and attenuates experimental lung metastasis in a xenograft mouse model. Correlation between SLUG and SOX9 levels was observed remarkably, we therefore sought to explore their mechanistic relationship and regulation. SLUG, beyond its known function as an epithelial-mesenchymal transition transcription factor, was found to regulate SOX9 by controlling its stability via a post-translational modification process. SLUG interacts directly with SOX9 and prevents it from ubiquitin-mediated proteasomal degradation. SLUG expression and binding are necessary for SOX9 promotion of lung CSCs and metastasis in a mouse model. Together, our findings provide a novel mechanistic insight into the regulation of CSCs via SLUG-SOX9 regulatory axis, which represents a potential novel target for CSC therapy that may overcome cancer chemoresistance and relapse. |
format | Online Article Text |
id | pubmed-4801727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48017272016-07-08 SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma Luanpitpong, Sudjit Li, Jingting Manke, Amruta Brundage, Kathleen Ellis, Emily McLaughlin, Sarah L. Angsutararux, Paweorn Chanthra, Nawin Voronkova, Maria Chen, Yi Charlie Wang, Liying Chanvorachote, Pithi Pei, Ming Issaragrisil, Surapol Rojanasakul, Yon Oncogene Article Cancer stem cells (CSCs) are a promising target for cancer therapy, particularly for metastatic lung cancers, but how CSCs are regulated is largely unknown. We identify two proteins, SLUG (encoded by SNAI2 gene) and SOX9, that are associated with advanced stage lung cancers and are implicated in the regulation of CSCs. Inhibition of either SLUG or SOX9 sufficiently inhibits CSCs in human lung cancer cells and attenuates experimental lung metastasis in a xenograft mouse model. Correlation between SLUG and SOX9 levels was observed remarkably, we therefore sought to explore their mechanistic relationship and regulation. SLUG, beyond its known function as an epithelial-mesenchymal transition transcription factor, was found to regulate SOX9 by controlling its stability via a post-translational modification process. SLUG interacts directly with SOX9 and prevents it from ubiquitin-mediated proteasomal degradation. SLUG expression and binding are necessary for SOX9 promotion of lung CSCs and metastasis in a mouse model. Together, our findings provide a novel mechanistic insight into the regulation of CSCs via SLUG-SOX9 regulatory axis, which represents a potential novel target for CSC therapy that may overcome cancer chemoresistance and relapse. 2015-09-21 2016-06-02 /pmc/articles/PMC4801727/ /pubmed/26387547 http://dx.doi.org/10.1038/onc.2015.351 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 Luanpitpong, Sudjit Li, Jingting Manke, Amruta Brundage, Kathleen Ellis, Emily McLaughlin, Sarah L. Angsutararux, Paweorn Chanthra, Nawin Voronkova, Maria Chen, Yi Charlie Wang, Liying Chanvorachote, Pithi Pei, Ming Issaragrisil, Surapol Rojanasakul, Yon SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title | SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title_full | SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title_fullStr | SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title_full_unstemmed | SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title_short | SLUG is required for SOX9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
title_sort | slug is required for sox9 stabilization and functions to promote cancer stem cells and metastasis in human lung carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801727/ https://www.ncbi.nlm.nih.gov/pubmed/26387547 http://dx.doi.org/10.1038/onc.2015.351 |
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