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ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L
Lung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324825/ https://www.ncbi.nlm.nih.gov/pubmed/34330894 http://dx.doi.org/10.1038/s41419-021-04043-6 |
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author | Zhang, Weijie Zhang, Ruochen Zeng, Yuanyuan Li, Yue Chen, Yikun Zhou, Jieqi Zhang, Yang Wang, Anqi Zhu, Jianjie Liu, Zeyi Yan, Zhaowei Huang, Jian-an |
author_facet | Zhang, Weijie Zhang, Ruochen Zeng, Yuanyuan Li, Yue Chen, Yikun Zhou, Jieqi Zhang, Yang Wang, Anqi Zhu, Jianjie Liu, Zeyi Yan, Zhaowei Huang, Jian-an |
author_sort | Zhang, Weijie |
collection | PubMed |
description | Lung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering β, β-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of β-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to β-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene β-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics. |
format | Online Article Text |
id | pubmed-8324825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83248252021-08-02 ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L Zhang, Weijie Zhang, Ruochen Zeng, Yuanyuan Li, Yue Chen, Yikun Zhou, Jieqi Zhang, Yang Wang, Anqi Zhu, Jianjie Liu, Zeyi Yan, Zhaowei Huang, Jian-an Cell Death Dis Article Lung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering β, β-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of β-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to β-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene β-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics. Nature Publishing Group UK 2021-07-31 /pmc/articles/PMC8324825/ /pubmed/34330894 http://dx.doi.org/10.1038/s41419-021-04043-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Weijie Zhang, Ruochen Zeng, Yuanyuan Li, Yue Chen, Yikun Zhou, Jieqi Zhang, Yang Wang, Anqi Zhu, Jianjie Liu, Zeyi Yan, Zhaowei Huang, Jian-an ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title | ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title_full | ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title_fullStr | ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title_full_unstemmed | ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title_short | ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L |
title_sort | alcap2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the e3 ligase nedd4l |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324825/ https://www.ncbi.nlm.nih.gov/pubmed/34330894 http://dx.doi.org/10.1038/s41419-021-04043-6 |
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