Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells
Mingyue Zhu1,2,*, Junli Guo1,2,*, Hua Xia1,3,*, Wei Li1,2, Yan Lu1,2, Xu Dong1,2, Yi Chen1,2, Xieju Xie1,2, Shigan Fu1,5 and Mengsen Li1,2,3,6
1 Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou, PR.China
2 Key Laboratory of Molecular Biology, Hainan Medical College, Haikou, PR.China
3 Graduate School, Guanxi Medical University, Nanning, PR. China
4 Department of Pathophysiology, Hainan Medical College, Haikou, PR.China
5 Department of Physiology, Hainan Medical College, Haikou, PR.China
6 Institution of Tumor, Hainan Medical College, Haikou, PR.China
* These authors contributed equally to this work
Correspondence:
Mengsen Li, email:
Keywords: Alpha fetoprotein, AKT/mTOR signal, CXCR4, Hepatocellular carcinoma, Metastasis
Received: December 10, 2014 Accepted: January 01, 2015 Published: January 06, 2015
Abstract
CXCR4, stromal cell-derived factor-1α(SDF 1α) receptor, stimulates growth and metastasis of hepatocellular carcinoma (HCC). Alpha-fetoprotein(AFP) governs the expression of some metastasis-related genes. Here we report that AFP and CXCR4 levels correlated in HCC tissues. AFP-expressing vectors induced CXCR4. In agreement, AFP depletion by siRNA decreased CXCR4. AFP co-localized and interacted with PTEN, thus inducing CXCR4 by activating AKT(Ser473) phosphorylation. In turn, phospho-mTOR(Ser2448) entered the nucleus and bound the CXCR4 gene promoter. Thus, AFP promoted migration of HCC cells. In concusion, AFP induced CXCR4 by activating the AKT/mTOR signal pathway.
