Li Chen, Wang Cong, Xing Yang, Zhen Jiaojiao, Ai Zhilong
Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Oncotarget. 2016 Apr 5;7(14):17751-9. doi: 10.18632/oncotarget.7474.
Gallbladder carcinoma (GBC) is the fifth most common malignancy of gastrointestinal tract. The prognosis of gallbladder carcinoma is extremely terrible partially due to metastasis. However, the mechanisms underlying gallbladder carcinoma metastasis remain largely unknown. CD133 is a widely used cancer stem cell marker including in gallbladder carcinoma. Here, we found that CD133 was highly expressed in gallbladder carcinoma as compared to normal tissues. CD133 was located in the invasive areas in gallbladder carcinoma. Down-regulation expression of CD133 inhibited migration and invasion of gallbladder carcinoma cell without obviously reducing cell proliferation. Mechanism analysis revealed that down-regulation expression of CD133 inhibited Akt phosphorylation and increased PTEN protein level. The inhibitory effect of CD133 down-regulation on gallbladder carcinoma cell migration could be rescued by Akt activation. Consistent with this, addition of Akt inhibitor Wortmannin markedly inhibited the migration ability of CD133-overexpressing cells. Thus, down-regulation of CD133 inhibits migration of gallbladder carcinoma cells through reducing Akt phosphorylation. These findings explore the fundamental biological aspect of CD133 in gallbladder carcinoma progression, providing insights into gallbladder carcinoma cell migration.
胆囊癌（GBC）是胃肠道第五大常见恶性肿瘤。胆囊癌的预后极其糟糕，部分原因是转移。然而，胆囊癌转移的潜在机制在很大程度上仍不清楚。CD133是一种广泛应用的癌症干细胞标志物，包括在胆囊癌中。在此，我们发现与正常组织相比，CD133在胆囊癌中高表达。CD133位于胆囊癌的侵袭区域。CD133的下调表达抑制了胆囊癌细胞的迁移和侵袭，而没有明显降低细胞增殖。机制分析表明，CD133的下调表达抑制了Akt磷酸化并增加了PTEN蛋白水平。CD133下调对胆囊癌细胞迁移的抑制作用可通过Akt激活来挽救。与此一致，添加Akt抑制剂渥曼青霉素显著抑制了CD133过表达细胞的迁移能力。因此，CD133的下调通过降低Akt磷酸化来抑制胆囊癌细胞的迁移。这些发现探索了CD133在胆囊癌进展中的基本生物学方面，为胆囊癌细胞迁移提供了见解。
