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 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.
Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
Zefeng
Z
Zhang
Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Xiaoling
X
Bu
Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Hao
H
Chen
Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Qiyi
Q
Wang
Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Weihong
W
Sha
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D045325:HCT116 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000473:pathology; D014410:Tumor Stem Cell Assay; D014945:Wound Healing
D015703:Antigens, CD; C069077:BMI1 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D063150:Polycomb Repressive Complex 1