Cargando…
Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells
Actomyosin-mediated contractility is required for the majority of force-driven cellular events such as cell division, adhesion, and migration. Under pathological conditions, the role of actomyosin contractility in malignant phenotypes of various solid tumors has been extensively discussed, but the p...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279019/ https://www.ncbi.nlm.nih.gov/pubmed/32422910 http://dx.doi.org/10.3390/ijms21103460 |
_version_ | 1783543466187292672 |
---|---|
author | Chang, Fengjiao Kong, So Jung Wang, Lele Choi, Beom K. Lee, Hyewon Kim, Chan Kim, Jin Man Park, Kyungpyo |
author_facet | Chang, Fengjiao Kong, So Jung Wang, Lele Choi, Beom K. Lee, Hyewon Kim, Chan Kim, Jin Man Park, Kyungpyo |
author_sort | Chang, Fengjiao |
collection | PubMed |
description | Actomyosin-mediated contractility is required for the majority of force-driven cellular events such as cell division, adhesion, and migration. Under pathological conditions, the role of actomyosin contractility in malignant phenotypes of various solid tumors has been extensively discussed, but the pathophysiological relevance in hematopoietic malignancies has yet to be elucidated. In this study, we found enhanced actomyosin contractility in diverse acute myeloid leukemia (AML) cell lines represented by highly expressed non-muscle myosin heavy chain A (NMIIA) and increased phosphorylation of the myosin regulatory light chain. Genetic and pharmacological inhibition of actomyosin contractility induced multivalent malignancy- suppressive effects in AML cells. In this context, perturbed actomyosin contractility enhances AML cell apoptosis through cytokinesis failure and aryl hydrocarbon receptor activation. Moreover, leukemic oncogenes were downregulated by the YAP/TAZ-mediated mechanotransduction pathway. Our results provide a theoretical background for targeting actomyosin contractility to suppress the malignancy of AML cells. |
format | Online Article Text |
id | pubmed-7279019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72790192020-06-15 Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells Chang, Fengjiao Kong, So Jung Wang, Lele Choi, Beom K. Lee, Hyewon Kim, Chan Kim, Jin Man Park, Kyungpyo Int J Mol Sci Article Actomyosin-mediated contractility is required for the majority of force-driven cellular events such as cell division, adhesion, and migration. Under pathological conditions, the role of actomyosin contractility in malignant phenotypes of various solid tumors has been extensively discussed, but the pathophysiological relevance in hematopoietic malignancies has yet to be elucidated. In this study, we found enhanced actomyosin contractility in diverse acute myeloid leukemia (AML) cell lines represented by highly expressed non-muscle myosin heavy chain A (NMIIA) and increased phosphorylation of the myosin regulatory light chain. Genetic and pharmacological inhibition of actomyosin contractility induced multivalent malignancy- suppressive effects in AML cells. In this context, perturbed actomyosin contractility enhances AML cell apoptosis through cytokinesis failure and aryl hydrocarbon receptor activation. Moreover, leukemic oncogenes were downregulated by the YAP/TAZ-mediated mechanotransduction pathway. Our results provide a theoretical background for targeting actomyosin contractility to suppress the malignancy of AML cells. MDPI 2020-05-14 /pmc/articles/PMC7279019/ /pubmed/32422910 http://dx.doi.org/10.3390/ijms21103460 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chang, Fengjiao Kong, So Jung Wang, Lele Choi, Beom K. Lee, Hyewon Kim, Chan Kim, Jin Man Park, Kyungpyo Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title | Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title_full | Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title_fullStr | Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title_full_unstemmed | Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title_short | Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells |
title_sort | targeting actomyosin contractility suppresses malignant phenotypes of acute myeloid leukemia cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279019/ https://www.ncbi.nlm.nih.gov/pubmed/32422910 http://dx.doi.org/10.3390/ijms21103460 |
work_keys_str_mv | AT changfengjiao targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT kongsojung targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT wanglele targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT choibeomk targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT leehyewon targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT kimchan targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT kimjinman targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells AT parkkyungpyo targetingactomyosincontractilitysuppressesmalignantphenotypesofacutemyeloidleukemiacells |