Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin.
Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin.
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DOI：
10.3892/ijmm.2016.2730
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发表时间：
2016-10
影响因子：
5.4
通讯作者：
Sha W
中科院分区：
文献类型：
--
作者：
Zhang Z;Bu X;Chen H;Wang Q;Sha W
转移和复发是癌症治疗的挑战。近年来，越来越多的证据表明，肿瘤干细胞（CSCs）和上皮间质转化（EMT）是肿瘤转移和复发的关键因素。致癌基因Bmi-1促进血液系统恶性肿瘤和许多实体瘤的发展。本研究的目的是利用HCT116结肠癌细胞系阐明Bmi-1促进结肠CSCs （CCSCs）侵袭和迁移的机制。采用成球培养基和磁活化细胞分选富集和筛选CCSCs。CD133和CD44被认为是CCSCs的标志物，它们在HCT116结肠癌细胞系中共表达。使用细胞计数试剂盒-8进行集落形成试验、细胞增殖试验和细胞活力试验以及注射CCSCs的裸鼠移植试验对CCSCs进行检测。CD133+CD44+ HCT116细胞克隆效率更高，增殖能力增强，细胞活力增强，致瘤性更强；这些细胞作为CCSCs用于后续实验。此外，用小干扰RNA （small interfering RNA, siRNA）沉默Bmi-1后，CD133+CD44+ HCT116细胞的侵袭和迁移能力明显下降。RT-qPCR和western blot结果显示，Bmi-1对E-cadherin的表达有负向影响。总的来说，我们的研究结果表明，Bmi-1通过下调E-cadherin来促进CCSCs的侵袭和迁移，可能是通过诱导EMT。因此，我们的研究结果表明，Bmi-1可能是治疗结肠癌的一个新的治疗靶点。
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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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
37.3
作者：
Dong P;Kaneuchi M;Watari H;Hamada J;Sudo S;Ju J;Sakuragi N
通讯作者：
Sakuragi N
影响因子：
29.4
作者：
Levin TG;Powell AE;Davies PS;Silk AD;Dismuke AD;Anderson EC;Swain JR;Wong MH
通讯作者：
Wong MH