Downregulation of p57 accelerates the growth and invasion of hepatocellular carcinoma

Abstract

p57 is a multifunctional protein involved in the regulation of tumor formation and development; however, the biological role of p57 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. To explore the role of p57 in the development of HCC, we examined p57 messenger RNA (mRNA) and protein levels in HCC tissues and adjacent non-cancerous tissues by immunohistochemistry, real-time polymerase chain reaction and western blot analysis. Moreover, we generated stable p57 knockdown HCC cell lines to investigate the impact of p57 downregulation on the growth and invasion of HCC in vitro and in vivo. Our results showed that p57 mRNA and protein levels were significantly decreased in human HCC tissues. In addition, this reduction in p57 expression was associated with increased tumor size, more advanced TNM stages, the presence of capsule invasion and extrahepatic metastasis and decreased overall survival time. In human HCC cell lines, p57 downregulation increased the expression of cyclin D1 and CDK2 and enhanced the activities of CDK4/cyclin D1 and CDK2/cyclin E complexes, resulting in increased cellular proliferation and growth of xenografts. Furthermore, p57 downregulation accelerated the invasion of HCC cells in vitro and in vivo by controlling the activity of LIMK1. In conclusion, the downregulation of p57 accelerates the growth and invasion of HCC, indicating that p57 is an important tumor suppressor in HCC. Based on these findings, p57 may be a potential target for HCC prevention and therapy.

P21‐Activated Kinase 4 Regulates the Cyclin‐Dependent Kinase Inhibitor P57Kip2 in Human Breast Cancer

“…The downregulation of p57 kip2 expression may be an important molecular event in tumor growth and invasion (Guo et al, 2011). The p57 kip2 gene has been suggested to be a tumor suppressor gene.…”

MicroRNA-21 inhibits p57Kip2 expression in prostate cancer

“…p57 Kip2 has been shown previously to act as a tumor suppressor gene by inhibiting cell migration and invasion [20]. Hence, we tested whether endogenous miR-21 functionally abrogated p57 Kip2 mediated tumor suppressive responses in prostate cancer cells.…”

Pyrrole-imidazole polyamide-mediated silencing of KCNQ1OT1 expression induces cell death in Wilms’ tumor cells

“…Accumulating evidence suggests that p57 KIP2 is one of Cip/Kip family of cyclin-dependent protein kinase inhibitor and blocks cell proliferation by inhibiting cell cycle progression (35). Additionally, p57 KIP2 has the ability to promote apoptosis and prohibit tissue invasion as well as metastasis (36,37). Therefore, we sought to examine whether the combinatory treatment of the PI polyamides could affect the expression level of the above-mentioned circumjacent genes including p57 KIP2 .…”