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Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1
Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, includ...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826015/ https://www.ncbi.nlm.nih.gov/pubmed/31578236 http://dx.doi.org/10.1242/jcs.234120 |
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author | Lorente, Mar García-Casas, Ana Salvador, Nélida Martínez-López, Angélica Gabicagogeascoa, Estibaliz Velasco, Guillermo López-Palomar, Lucía Castillo-Lluva, Sonia |
author_facet | Lorente, Mar García-Casas, Ana Salvador, Nélida Martínez-López, Angélica Gabicagogeascoa, Estibaliz Velasco, Guillermo López-Palomar, Lucía Castillo-Lluva, Sonia |
author_sort | Lorente, Mar |
collection | PubMed |
description | Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagy-mediated cancer cell death through increasing the expression of Tribbles pseudokinase 3 (TRIB3). Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation. |
format | Online Article Text |
id | pubmed-6826015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-68260152019-11-04 Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 Lorente, Mar García-Casas, Ana Salvador, Nélida Martínez-López, Angélica Gabicagogeascoa, Estibaliz Velasco, Guillermo López-Palomar, Lucía Castillo-Lluva, Sonia J Cell Sci Research Article Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagy-mediated cancer cell death through increasing the expression of Tribbles pseudokinase 3 (TRIB3). Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation. The Company of Biologists Ltd 2019-10-15 2019-10-22 /pmc/articles/PMC6826015/ /pubmed/31578236 http://dx.doi.org/10.1242/jcs.234120 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Lorente, Mar García-Casas, Ana Salvador, Nélida Martínez-López, Angélica Gabicagogeascoa, Estibaliz Velasco, Guillermo López-Palomar, Lucía Castillo-Lluva, Sonia Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title | Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title_full | Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title_fullStr | Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title_full_unstemmed | Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title_short | Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1 |
title_sort | inhibiting sumo1-mediated sumoylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via rac1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826015/ https://www.ncbi.nlm.nih.gov/pubmed/31578236 http://dx.doi.org/10.1242/jcs.234120 |
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