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Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1
Breast cancer is the leading cause of cancer-related deaths in the United States. The majority of deaths (90%) in breast cancer patients is caused by invasion and metastasis–two features related to the epithelial-to-mesenchymal transition (EMT). Twist1 is a key transcription factor that promotes the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904211/ https://www.ncbi.nlm.nih.gov/pubmed/33626096 http://dx.doi.org/10.1371/journal.pone.0247652 |
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author | Nafie, Ebtesam Lolarga, Jade Lam, Brandon Guo, Jonathan Abdollahzadeh, Elnaz Rodriguez, Sandy Glackin, Carlotta Liu, Junjun |
author_facet | Nafie, Ebtesam Lolarga, Jade Lam, Brandon Guo, Jonathan Abdollahzadeh, Elnaz Rodriguez, Sandy Glackin, Carlotta Liu, Junjun |
author_sort | Nafie, Ebtesam |
collection | PubMed |
description | Breast cancer is the leading cause of cancer-related deaths in the United States. The majority of deaths (90%) in breast cancer patients is caused by invasion and metastasis–two features related to the epithelial-to-mesenchymal transition (EMT). Twist1 is a key transcription factor that promotes the EMT, which leads to cell migration, invasion, cancer metastasis, and therapeutic resistance. Harmine is a beta-carboline alkaloid found in a variety of plants and was recently shown to be able to induce degradation of Twist Family BHLH Transcription Factor 1 (Twist1) in non-small cell lung cancer cells (NSCLC). In this study, we show that harmine can inhibit migration and invasion of both human and mouse breast cancer cells in a dose-dependent manner. Further study shows that this inhibition is most likely achieved by inducing a proteasome-dependent Twist1 degradation. At the concentrations tested, harmine did not affect the viability of cells significantly, suggesting that its inhibition of cancer cell migration and invasion is largely independent of its cytotoxicity, but due to its ability to affect regulators of EMT such as Twist1. This result may facilitate the development of strategies that target Twist1 to treat metastatic breast cancer, as Twist1 is expressed at a high level in metastatic breast cancer cells but not in normal cells. |
format | Online Article Text |
id | pubmed-7904211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79042112021-03-03 Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 Nafie, Ebtesam Lolarga, Jade Lam, Brandon Guo, Jonathan Abdollahzadeh, Elnaz Rodriguez, Sandy Glackin, Carlotta Liu, Junjun PLoS One Research Article Breast cancer is the leading cause of cancer-related deaths in the United States. The majority of deaths (90%) in breast cancer patients is caused by invasion and metastasis–two features related to the epithelial-to-mesenchymal transition (EMT). Twist1 is a key transcription factor that promotes the EMT, which leads to cell migration, invasion, cancer metastasis, and therapeutic resistance. Harmine is a beta-carboline alkaloid found in a variety of plants and was recently shown to be able to induce degradation of Twist Family BHLH Transcription Factor 1 (Twist1) in non-small cell lung cancer cells (NSCLC). In this study, we show that harmine can inhibit migration and invasion of both human and mouse breast cancer cells in a dose-dependent manner. Further study shows that this inhibition is most likely achieved by inducing a proteasome-dependent Twist1 degradation. At the concentrations tested, harmine did not affect the viability of cells significantly, suggesting that its inhibition of cancer cell migration and invasion is largely independent of its cytotoxicity, but due to its ability to affect regulators of EMT such as Twist1. This result may facilitate the development of strategies that target Twist1 to treat metastatic breast cancer, as Twist1 is expressed at a high level in metastatic breast cancer cells but not in normal cells. Public Library of Science 2021-02-24 /pmc/articles/PMC7904211/ /pubmed/33626096 http://dx.doi.org/10.1371/journal.pone.0247652 Text en © 2021 Nafie et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Nafie, Ebtesam Lolarga, Jade Lam, Brandon Guo, Jonathan Abdollahzadeh, Elnaz Rodriguez, Sandy Glackin, Carlotta Liu, Junjun Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title | Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title_full | Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title_fullStr | Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title_full_unstemmed | Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title_short | Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1 |
title_sort | harmine inhibits breast cancer cell migration and invasion by inducing the degradation of twist1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904211/ https://www.ncbi.nlm.nih.gov/pubmed/33626096 http://dx.doi.org/10.1371/journal.pone.0247652 |
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