Research Papers:

CD133 promotes gallbladder carcinoma cell migration through activating Akt phosphorylation

Chen Li, Cong Wang, Yang Xing, Jiaojiao Zhen and Zhilong Ai _

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Oncotarget. 2016; 7:17751-17759. https://doi.org/10.18632/oncotarget.7474

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Chen Li1,*, Cong Wang1,*, Yang Xing2,*, Jiaojiao Zhen1, Zhilong Ai1

1Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China

2Key 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

*These authors contributed equally to this work

Correspondence to:

Zhilong Ai, e-mail: ai.zhilong@zs-hospital.sh.cn

Keywords: CD133, gallbladder carcinoma, migration, invasion, Akt pathway

Received: June 18, 2015     Accepted: January 27, 2016     Published: February 18, 2016


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.

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