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MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway
MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been impl...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996672/ https://www.ncbi.nlm.nih.gov/pubmed/24504508 |
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author | Bouillez, Audrey Gnemmi, Viviane Gaudelot, Kelly Hémon, Brigitte Ringot, Bélinda Pottier, Nicolas Glowacki, François Butruille, Caroline Cauffiez, Christelle Hamdane, Malika Sergeant, Nicolas Seuningen, Isabelle Van Leroy, Xavier Aubert, Sébastien Perrais, Michaël |
author_facet | Bouillez, Audrey Gnemmi, Viviane Gaudelot, Kelly Hémon, Brigitte Ringot, Bélinda Pottier, Nicolas Glowacki, François Butruille, Caroline Cauffiez, Christelle Hamdane, Malika Sergeant, Nicolas Seuningen, Isabelle Van Leroy, Xavier Aubert, Sébastien Perrais, Michaël |
author_sort | Bouillez, Audrey |
collection | PubMed |
description | MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been implicated in the hypoxic pathway, the main renal carcinogenetic pathway. In this context, we assessed the effects of MUC1 overexpression on renal cancer cells properties. Using shRNA strategy and/or different MUC1 constructs, we found that MUC1-extracellular domain and MUC1-CT are involved in increase of migration, cell viability, resistance to anoikis and in decrease of cell aggregation in cancer cells. Invasiveness depends only on MUC1-CT. Then, by using siRNA strategy and/or pharmacological inhibitors or peptides, we showed that sheddases ADAM10, ADAM17 and gamma-secretase are necessary for MUC1 C-terminal subunit (MUC1-C) nuclear location and in increase of invasion property. Finally, MUC1 overexpression increases ADAM10/17 protein expression suggesting a positive regulatory loop. In conclusion, we report that MUC1 acts in renal cancer progression and MUC1-C nuclear localization drives invasiveness of cancer cells through a sheddase/gamma secretase dependent pathway. MUC1 appears as a therapeutic target by blocking MUC1 cleavage or nuclear translocation by using pharmacological approach and peptide strategies. |
format | Online Article Text |
id | pubmed-3996672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-39966722014-04-23 MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway Bouillez, Audrey Gnemmi, Viviane Gaudelot, Kelly Hémon, Brigitte Ringot, Bélinda Pottier, Nicolas Glowacki, François Butruille, Caroline Cauffiez, Christelle Hamdane, Malika Sergeant, Nicolas Seuningen, Isabelle Van Leroy, Xavier Aubert, Sébastien Perrais, Michaël Oncotarget Research Paper MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been implicated in the hypoxic pathway, the main renal carcinogenetic pathway. In this context, we assessed the effects of MUC1 overexpression on renal cancer cells properties. Using shRNA strategy and/or different MUC1 constructs, we found that MUC1-extracellular domain and MUC1-CT are involved in increase of migration, cell viability, resistance to anoikis and in decrease of cell aggregation in cancer cells. Invasiveness depends only on MUC1-CT. Then, by using siRNA strategy and/or pharmacological inhibitors or peptides, we showed that sheddases ADAM10, ADAM17 and gamma-secretase are necessary for MUC1 C-terminal subunit (MUC1-C) nuclear location and in increase of invasion property. Finally, MUC1 overexpression increases ADAM10/17 protein expression suggesting a positive regulatory loop. In conclusion, we report that MUC1 acts in renal cancer progression and MUC1-C nuclear localization drives invasiveness of cancer cells through a sheddase/gamma secretase dependent pathway. MUC1 appears as a therapeutic target by blocking MUC1 cleavage or nuclear translocation by using pharmacological approach and peptide strategies. Impact Journals LLC 2014-02-02 /pmc/articles/PMC3996672/ /pubmed/24504508 Text en Copyright: © 2014 Bouillez et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bouillez, Audrey Gnemmi, Viviane Gaudelot, Kelly Hémon, Brigitte Ringot, Bélinda Pottier, Nicolas Glowacki, François Butruille, Caroline Cauffiez, Christelle Hamdane, Malika Sergeant, Nicolas Seuningen, Isabelle Van Leroy, Xavier Aubert, Sébastien Perrais, Michaël MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title | MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title_full | MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title_fullStr | MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title_full_unstemmed | MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title_short | MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
title_sort | muc1-c nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996672/ https://www.ncbi.nlm.nih.gov/pubmed/24504508 |
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