Alpha-fetoprotein receptor as an early indicator of HBx-driven hepatocarcinogenesis and its applications in tracing cancer cell metastasis

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

“…Interestingly, in this study, ChIP with p-mTOR(Ser2448) as a target showed a physical interaction between p-mTOR(Ser2448) and the CXCR4 gene promoter when HLE cells were transfected with an AFP-expressing vectors that could be abolished by the silencing of AFP in PLC/PRF/5 cells, thereby providing the direct evidence that cytoplasmic AFP acts as a key regulator in the modulation of CXCR4 expression via activating the AKT/mTOR signaling pathway. Some studies have shown that CXCR4 plays a pivotal role in on metastasis of cancer cell[33,34], while we found that AFP stimulated CXCR4 expression by activating PI3K/AKT signaling[31]. In this study, the results also indicated that AFP harbors a function to stimulate migration of HCC, this investigation demonstrated that AFP promoted expression of CXCR4 contributes to metastasis of HCC cells.…”

“…Moreover, Dubrovska et al[30] demonstrated the direct regulation of CXCR4 expression by the PI3K pathway and thus implied a mutually positive regulatory feedback loop between the PI3K/AKT and CXCR4/CXCL12 signaling pathways, which are both important for cancer metastasis. Furthermore, our previous results indicated that HBV-X protein induced the expression of AFP in human normal liver cells, which correlated to CXCR4 expression in human hepatoma cells[31], and accumulated evidences showed that the mTOR/CXCR4 signal axis is closely associated with the promotion of cancer cell metastasis[32]. In the present study, we also explored the possible mechanisms by which AFP can regulate CXCR4 expression via knockdown of AFP in PLC/PRF/5 cells or appearance of AFP in pcDNA3.1- afp vectors transfected HLE cells.…”

HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway

“…The results demonstrated that HBV(+)/AFP(+) HCC tissues expressed higher levels of the reprogramming‐related proteins Oct4, Klf4, Sox2 and c‐myc and the stem cell markers CD44, CD133, EpCAM compared to HBV(−)/AFP(−) HCC tissues and normal liver tissues, suggesting that AFP expression closely correlated with presence of CSCs. We had previously found that HBx drives AFP expression to stimulate the expression of Ras and Src, and AFP mediated HBx‐induced hepatocarcinogenesis . These data indicate that HBx promotes AFP expression and plays a pivotal role in HCC development.…”

C-terminal-truncated hepatitis B virus X protein enhances the development of diethylnitrosamine-induced hepatocellular carcinogenesis

“…In addition, we showed that AFP, an important biomarker of HCC, was highly expressed in treated transgenic mice at 12 months. It was demonstrated that HBx derepresses AFP expression through its interaction with p53 and that the expression of AFP receptor was a pivotal event for HBx inducing malignant transformation of liver cells (Li et al, 2013;Ogden et al, 2000).…”