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SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation
TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 e...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935229/ https://www.ncbi.nlm.nih.gov/pubmed/35342335 http://dx.doi.org/10.7150/ijbs.60594 |
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author | Gao, Yongchang Wang, Rongrong Liu, Jianjing Zhao, Ke Qian, Xiaolong He, Xianghui Liu, Hong |
author_facet | Gao, Yongchang Wang, Rongrong Liu, Jianjing Zhao, Ke Qian, Xiaolong He, Xianghui Liu, Hong |
author_sort | Gao, Yongchang |
collection | PubMed |
description | TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment. |
format | Online Article Text |
id | pubmed-8935229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-89352292022-03-24 SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation Gao, Yongchang Wang, Rongrong Liu, Jianjing Zhao, Ke Qian, Xiaolong He, Xianghui Liu, Hong Int J Biol Sci Research Paper TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment. Ivyspring International Publisher 2022-03-06 /pmc/articles/PMC8935229/ /pubmed/35342335 http://dx.doi.org/10.7150/ijbs.60594 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Gao, Yongchang Wang, Rongrong Liu, Jianjing Zhao, Ke Qian, Xiaolong He, Xianghui Liu, Hong SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title | SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title_full | SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title_fullStr | SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title_full_unstemmed | SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title_short | SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation |
title_sort | senp1 promotes triple-negative breast cancer invasion and metastasis via enhancing csn5 transcription mediated by gata1 desumoylation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935229/ https://www.ncbi.nlm.nih.gov/pubmed/35342335 http://dx.doi.org/10.7150/ijbs.60594 |
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