The role of cytoplasmic p57 in invasion of hepatocellular carcinoma

Background: Our previous research suggested that p57 downregulation could accelerate the growth and invasion of hepatocellular carcinoma in vitro and in vivo. Aim: To evaluate the role of cytoplasmic p57 and its regulatory mechanism during hepatocellular carcinoma invasion. Methods: We examined the subcellular localization of p57 by immunohistochemistry in 45 pairs of cancerous tissues and adjacent non-cancerous tissues. Moreover, we generated stable p57 knockdown hepatoma cell lines to investigate the mechanism of cytoplasmic p57-mediated regulation of invasion by immunoprecipitation, confocal immunofluorescence microscopy and western blot of nuclear and cytoplasmic extracts. Results: Our results showed that cytoplasmic expression of p57 was reduced in specimens from patients with capsular invasion and metastasis (P < 0.05). Moreover, the level of p-cofilin was decreased in the group lacking cytoplasmic p57 expression (P < 0.05). Co-expression of p57 and p-cofilin was reduced in specimens from patients with tumors at later stages (III + IV), tumors showing capsular invasion and metastatic tumors. We further observed that p57 downregulation decreased the assembly of p57 and LIM domain kinase 1 and its kinase activity, subsequently reducing the level of p-cofilin in the cytoplasm. Conclusions: Cytoplasmic p57 might be a key regulator in hepatocellular carcinoma invasion via the LIM domain kinase 1/p-cofilin pathway.