Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells

Mingyue Zhu; Junli Guo; Hua Xia; Wei Li; Yan Lu; Xu Dong; Yi Chen; Xieju Xie; Shigan Fu; Mengsen Li

doi:10.18632/oncoscience.115

Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells

Oncoscience. 2015 Jan 6;2(1):59-70. doi: 10.18632/oncoscience.115. eCollection 2015.

Authors

Mingyue Zhu^#^{1

2}, Junli Guo^#^{1

2}, Hua Xia^#^{1

3}, Wei Li^{1

2}, Yan Lu^{1

2}, Xu Dong^{1

2}, Yi Chen^{1

2}, Xieju Xie^{1

2}, Shigan Fu^{1

4}, Mengsen Li^{1

2

3

5}

Affiliations

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 Physiology, Hainan Medical College, Haikou, PR.China.
⁵ Institution of Tumor, Hainan Medical College, Haikou, PR.China.

^# Contributed equally.

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.

Keywords: AKT/mTOR signal; Alpha fetoprotein; CXCR4; Hepatocellular carcinoma; Metastasis.