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

• Published in: International journal of molecular medicine Vol. 38; no. 4; pp. 1199 - 1207
• Main Authors: Zhang, Zefeng, Bu, Xiaoling, Chen, Hao, Wang, Qiyi, Sha, Weihong
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Animals; Antigens, CD - metabolism; Bmi-1; Brain cancer; Breast cancer; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cancer therapies; Care and treatment; Cell Count; Cell Movement; Cell Proliferation; Cell Survival; Colon cancer; colon cancer stem cells; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Colorectal cancer; Development and progression; Down-Regulation; E-cadherin; Flow Cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Gene Silencing; Genetic aspects; Growth factors; HCT116 Cells; Health aspects; Humans; Metastasis; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Transplantation; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Oncogenes; Pathogenesis; Polycomb Repressive Complex 1 - metabolism; Properties; Rodents; Spheroids, Cellular - pathology; Tumor Stem Cell Assay; Tumors; Wound Healing; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2016.2730

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.