Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin

Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic ma...

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Autores principales: Zhang, Zefeng, Bu, Xiaoling, Chen, Hao, Wang, Qiyi, Sha, Weihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029956/
https://www.ncbi.nlm.nih.gov/pubmed/27600678
http://dx.doi.org/10.3892/ijmm.2016.2730
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author Zhang, Zefeng
Bu, Xiaoling
Chen, Hao
Wang, Qiyi
Sha, Weihong
author_facet Zhang, Zefeng
Bu, Xiaoling
Chen, Hao
Wang, Qiyi
Sha, Weihong
author_sort Zhang, Zefeng
collection PubMed
description Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line. Sphere formation medium and magnetic-activated cell sorting were used to enrich and screen the CCSCs. CD133 and CD44 were regarded as markers of CCSCs and they were found to be co-expressed in the HCT116 colon cancer cell line. Colony formation assay, cell proliferation assay and viability assay using the Cell Counting Kit-8, and transplantation assay using nude mice injected with CCSCs were used to examine the CCSCs. The CD133(+)CD44(+) HCT116 cells exhibited greater cloning efficiency, an enhanced proliferative ability, increased cell viability and stronger tumorigenicity; these cells were used as the CCSCs for subsequent experiments. In addition, the invasive and migratory abilities of the CD133(+)CD44(+) HCT116 cells were markedly decreased when Bmi-1 was silenced by small interfering RNA (siRNA). The results of RT-qPCR and western blot analysis suggested that Bmi-1 had a negative effect on E-cadherin expression. On the whole, our findings suggest that Bmi-1 promotes the invasion and migration of CCSCs through the downregulation of E-cadherin, possibly by inducing EMT. Our findings thus indicate that Bmi-1 may be a novel therapeutic target for the treatment of colon cancer.
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spelling pubmed-50299562016-09-22 Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin Zhang, Zefeng Bu, Xiaoling Chen, Hao Wang, Qiyi Sha, Weihong Int J Mol Med Articles Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line. Sphere formation medium and magnetic-activated cell sorting were used to enrich and screen the CCSCs. CD133 and CD44 were regarded as markers of CCSCs and they were found to be co-expressed in the HCT116 colon cancer cell line. Colony formation assay, cell proliferation assay and viability assay using the Cell Counting Kit-8, and transplantation assay using nude mice injected with CCSCs were used to examine the CCSCs. The CD133(+)CD44(+) HCT116 cells exhibited greater cloning efficiency, an enhanced proliferative ability, increased cell viability and stronger tumorigenicity; these cells were used as the CCSCs for subsequent experiments. In addition, the invasive and migratory abilities of the CD133(+)CD44(+) HCT116 cells were markedly decreased when Bmi-1 was silenced by small interfering RNA (siRNA). The results of RT-qPCR and western blot analysis suggested that Bmi-1 had a negative effect on E-cadherin expression. On the whole, our findings suggest that Bmi-1 promotes the invasion and migration of CCSCs through the downregulation of E-cadherin, possibly by inducing EMT. Our findings thus indicate that Bmi-1 may be a novel therapeutic target for the treatment of colon cancer. D.A. Spandidos 2016-10 2016-09-07 /pmc/articles/PMC5029956/ /pubmed/27600678 http://dx.doi.org/10.3892/ijmm.2016.2730 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhang, Zefeng
Bu, Xiaoling
Chen, Hao
Wang, Qiyi
Sha, Weihong
Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title_full Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title_fullStr Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title_full_unstemmed Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title_short Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin
title_sort bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of e-cadherin
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029956/
https://www.ncbi.nlm.nih.gov/pubmed/27600678
http://dx.doi.org/10.3892/ijmm.2016.2730
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