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ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer
The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by cont...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142079/ https://www.ncbi.nlm.nih.gov/pubmed/32269211 http://dx.doi.org/10.1038/s41419-020-2415-2 |
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author | Liu, Dian Ertay, Ayse Hill, Charlotte Zhou, Yilu Li, Juanjuan Zou, Yanmei Qiu, Hong Yuan, Xianglin Ewing, Rob M. Lu, Xin Xiong, Hua Wang, Yihua |
author_facet | Liu, Dian Ertay, Ayse Hill, Charlotte Zhou, Yilu Li, Juanjuan Zou, Yanmei Qiu, Hong Yuan, Xianglin Ewing, Rob M. Lu, Xin Xiong, Hua Wang, Yihua |
author_sort | Liu, Dian |
collection | PubMed |
description | The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients. |
format | Online Article Text |
id | pubmed-7142079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71420792020-04-13 ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer Liu, Dian Ertay, Ayse Hill, Charlotte Zhou, Yilu Li, Juanjuan Zou, Yanmei Qiu, Hong Yuan, Xianglin Ewing, Rob M. Lu, Xin Xiong, Hua Wang, Yihua Cell Death Dis Article The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients. Nature Publishing Group UK 2020-04-08 /pmc/articles/PMC7142079/ /pubmed/32269211 http://dx.doi.org/10.1038/s41419-020-2415-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Liu, Dian Ertay, Ayse Hill, Charlotte Zhou, Yilu Li, Juanjuan Zou, Yanmei Qiu, Hong Yuan, Xianglin Ewing, Rob M. Lu, Xin Xiong, Hua Wang, Yihua ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title | ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title_full | ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title_fullStr | ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title_full_unstemmed | ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title_short | ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
title_sort | aspp1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142079/ https://www.ncbi.nlm.nih.gov/pubmed/32269211 http://dx.doi.org/10.1038/s41419-020-2415-2 |
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