14-3-3β Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells by Modulating Expression of MMP2 and MMP9 through PI3K/Akt/NF-κB Pathway

14-3-3 beta has been demonstrated to possess the oncogenic potential, and its increased expression has been detected in multiple types of carcinomas. However, majority of previous studies focused on the role of 14-3-3 beta in tumor cell proliferation and apoptosis, leaving much to be elucidated about its function in tumor cell invasion and metastasis. Hence, the present study aimed to investigate the role of 14-3-3 beta in the invasion of hepatocellular carcinoma (HCC) cells and the implications in the prognosis of HCC patients. We first examined the expression of 14-3-3 beta in the primary tumors of HCC patients with or without portal vein tumor thrombus (PVTT), and found that 14-3-3 beta expression was higher in the primary tumors with PVTT, and the level was even higher in the PVTTs. Kaplan-Meier curves and multivariate analysis revealed that high expression of 14-3-3 beta was associated with overall survival (OS) and time to recurrence (TTR) of HCC patients. In addition, ectopic expression of 14-3-3 beta in HCC cell lines led to enhanced migration ability and invasiveness, as well as up-regulation of matrix metalloproteinase 2 and 9, which could be suppressed by inhibiting the activation of Akt and nuclear factor-kappa B (NF-kappa B) signaling. Furthermore, we identified a correlated elevation of 14-3-3 beta and p-Akt in the primary tumors of HCC patients, and showed that a combinatory detection of 14-3-3 beta and p-Akt could better predict post-surgical outcome of HCC patients.