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CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling

CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter ove...

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Autores principales: Chen, Wei-Liang, Huang, Ai-Fang, Huang, Shih-Ming, Ho, Ching-Liang, Chang, Yung-Lung, Chan, James Yi-Hsin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589567/
https://www.ncbi.nlm.nih.gov/pubmed/28903328
http://dx.doi.org/10.18632/oncotarget.11132
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author Chen, Wei-Liang
Huang, Ai-Fang
Huang, Shih-Ming
Ho, Ching-Liang
Chang, Yung-Lung
Chan, James Yi-Hsin
author_facet Chen, Wei-Liang
Huang, Ai-Fang
Huang, Shih-Ming
Ho, Ching-Liang
Chang, Yung-Lung
Chan, James Yi-Hsin
author_sort Chen, Wei-Liang
collection PubMed
description CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter overall survival in lung cancer. However, no data are available regarding the clinical significance of CD164 expression in lung cancer. This study explores whether CD164 promotes tumor-initiation and drug resistance through the stem cell property. Using tissue microarrays, we determine that CD164 expression is correlated with clinicopathological characteristics in human lung cancer. The CD164 overexpression in normal lung epithelial cells (BEAS2B cells) leads to malignant transformation in vitro, tumorigenicity in xenografted mice, stem cell-like property, and drug resistance through ATP-binding cassette transporters. The CD164 overexpression increases CXCR4 expression and activates Akt/mTOR signaling. Rapamycin, an mTOR inhibitor, hinders cell proliferation along with sphere formation in vitro and impedes tumor growth in vivo. In conclusion, we have provided evidence that CD164 promotes the growth of lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell therapeutic marker may develop an effective therapy in patients with chemoresistant lung cancer.
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spelling pubmed-55895672017-09-12 CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling Chen, Wei-Liang Huang, Ai-Fang Huang, Shih-Ming Ho, Ching-Liang Chang, Yung-Lung Chan, James Yi-Hsin Oncotarget Research Paper CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter overall survival in lung cancer. However, no data are available regarding the clinical significance of CD164 expression in lung cancer. This study explores whether CD164 promotes tumor-initiation and drug resistance through the stem cell property. Using tissue microarrays, we determine that CD164 expression is correlated with clinicopathological characteristics in human lung cancer. The CD164 overexpression in normal lung epithelial cells (BEAS2B cells) leads to malignant transformation in vitro, tumorigenicity in xenografted mice, stem cell-like property, and drug resistance through ATP-binding cassette transporters. The CD164 overexpression increases CXCR4 expression and activates Akt/mTOR signaling. Rapamycin, an mTOR inhibitor, hinders cell proliferation along with sphere formation in vitro and impedes tumor growth in vivo. In conclusion, we have provided evidence that CD164 promotes the growth of lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell therapeutic marker may develop an effective therapy in patients with chemoresistant lung cancer. Impact Journals LLC 2016-08-09 /pmc/articles/PMC5589567/ /pubmed/28903328 http://dx.doi.org/10.18632/oncotarget.11132 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Wei-Liang
Huang, Ai-Fang
Huang, Shih-Ming
Ho, Ching-Liang
Chang, Yung-Lung
Chan, James Yi-Hsin
CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title_full CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title_fullStr CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title_full_unstemmed CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title_short CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling
title_sort cd164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via akt/mtor signaling
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589567/
https://www.ncbi.nlm.nih.gov/pubmed/28903328
http://dx.doi.org/10.18632/oncotarget.11132
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