Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nafie, Ebtesam, Lolarga, Jade, Lam, Brandon, Guo, Jonathan, Abdollahzadeh, Elnaz, Rodriguez, Sandy, Glackin, Carlotta, Liu, Junjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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
_version_ 1783654884852105216
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
work_keys_str_mv AT nafieebtesam harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT lolargajade harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT lambrandon harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT guojonathan harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT abdollahzadehelnaz harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT rodriguezsandy harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT glackincarlotta harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1
AT liujunjun harmineinhibitsbreastcancercellmigrationandinvasionbyinducingthedegradationoftwist1