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Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm
BACKGROUND: Cancer stem cells (CSCs) are regarded as the root of tumor progression, thus representing an anti-cancer therapy through targeting this cell sub-population. METHODS: Non-small cell lung cancer (NSCLC) CSCs were enriched by non-adherent spheroid formation analysis. Lentivirus infection wa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325009/ https://www.ncbi.nlm.nih.gov/pubmed/32612672 http://dx.doi.org/10.1186/s13020-020-00348-4 |
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author | Jin, Linling Wu, Zhenzhen Wang, Yanli Zhao, Xin |
author_facet | Jin, Linling Wu, Zhenzhen Wang, Yanli Zhao, Xin |
author_sort | Jin, Linling |
collection | PubMed |
description | BACKGROUND: Cancer stem cells (CSCs) are regarded as the root of tumor progression, thus representing an anti-cancer therapy through targeting this cell sub-population. METHODS: Non-small cell lung cancer (NSCLC) CSCs were enriched by non-adherent spheroid formation analysis. Lentivirus infection was used to stably change gene expression. Cell cycle, EdU incorporation, cell apoptosis, cell viability, ALDH1 activity, spheroid formation and in vivo tumor initiation assays were performed to detect the effects of Cryptotanshinone (CT), a traditional Chinese herb medicine, on the stemness of NSCLC cells. RNA-sequencing combined qRT-PCR and western blot analysis were constructed to explore the underlying mechanism contributing to CT-mediated effects. RESULTS: CT could attenuate the stemness of NSCLC CSCs, as evident by the reduced spheroid formation ability, stemness marker expression and ALDH1 activity. Additionally, CT provoked NSCLC CSCs entry into the cell cycle. RNA-sequencing analysis showed that Hippo signaling pathway was highly enriched in NSCLC CSCs with CT treatment. Further experiments disclosed that CT decreased TAZ (a regulatory master of Hippo pathway) expression via promoting its nuclear-cytoplasm translocation in NSCLC CSCs. Also, overexpression of TAZ partially saved the attenuation of CT on the stemness of NSCLC CSCs. Notably, CT enhanced the sensitivity of tyrosine kinase inhibitor (TKI) and chemotherapy in NSCLC CSCs. CONCLUSIONS: This work reveals that CT attenuates NSCLC CSC stemness, implying the possibility of CT as an adjuvant therapy for NSCLC. |
format | Online Article Text |
id | pubmed-7325009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-73250092020-06-30 Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm Jin, Linling Wu, Zhenzhen Wang, Yanli Zhao, Xin Chin Med Research BACKGROUND: Cancer stem cells (CSCs) are regarded as the root of tumor progression, thus representing an anti-cancer therapy through targeting this cell sub-population. METHODS: Non-small cell lung cancer (NSCLC) CSCs were enriched by non-adherent spheroid formation analysis. Lentivirus infection was used to stably change gene expression. Cell cycle, EdU incorporation, cell apoptosis, cell viability, ALDH1 activity, spheroid formation and in vivo tumor initiation assays were performed to detect the effects of Cryptotanshinone (CT), a traditional Chinese herb medicine, on the stemness of NSCLC cells. RNA-sequencing combined qRT-PCR and western blot analysis were constructed to explore the underlying mechanism contributing to CT-mediated effects. RESULTS: CT could attenuate the stemness of NSCLC CSCs, as evident by the reduced spheroid formation ability, stemness marker expression and ALDH1 activity. Additionally, CT provoked NSCLC CSCs entry into the cell cycle. RNA-sequencing analysis showed that Hippo signaling pathway was highly enriched in NSCLC CSCs with CT treatment. Further experiments disclosed that CT decreased TAZ (a regulatory master of Hippo pathway) expression via promoting its nuclear-cytoplasm translocation in NSCLC CSCs. Also, overexpression of TAZ partially saved the attenuation of CT on the stemness of NSCLC CSCs. Notably, CT enhanced the sensitivity of tyrosine kinase inhibitor (TKI) and chemotherapy in NSCLC CSCs. CONCLUSIONS: This work reveals that CT attenuates NSCLC CSC stemness, implying the possibility of CT as an adjuvant therapy for NSCLC. BioMed Central 2020-06-30 /pmc/articles/PMC7325009/ /pubmed/32612672 http://dx.doi.org/10.1186/s13020-020-00348-4 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jin, Linling Wu, Zhenzhen Wang, Yanli Zhao, Xin Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title | Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title_full | Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title_fullStr | Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title_full_unstemmed | Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title_short | Cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting TAZ translocation from nuclear to cytoplasm |
title_sort | cryptotanshinone attenuates the stemness of non-small cell lung cancer cells via promoting taz translocation from nuclear to cytoplasm |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325009/ https://www.ncbi.nlm.nih.gov/pubmed/32612672 http://dx.doi.org/10.1186/s13020-020-00348-4 |
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