Part of the book: Targets in Gene Therapy
Oncogenic secretory clusterin (sCLU) is a stress-induced molecular chaperone that confers proliferative and survival advantages to hepatocellular carcinoma (HCC), plays a crucial role in cell proliferation, multiple drug resistance, metastasis, and tumor progression. However, the targeted effects and molecular mechanisms of sCLU for malignant tumor are still unknown. This chapter aims to review some progression of oncogenic sCLU as a promising therapeutic target for HCC. An English-language literature search was conducted using bibliographic databases on some valuable articles in focused review questions to analyze the interventions and findings of included studies using a conceptual framework. The positive rate of hepatic sCLU expression in cancerous tissues was significantly higher more than that in their surrounding non-cancerous ones at gene transcription level or at protein level, with increasing according to tumor-node-metastasis (TNM) staging. Abnormal expression of oncogenic sCLU associated with poor differentiation degree and TNM stage of HCC also has been considered as a valuable diagnostic or independent prognostic biomarker for HCC. Furthermore, silencing sCLU at mRNA level by specific shRNA or inhibition by OGX-011 suppressed the colony formation and proliferation of tumor cells with apoptosis increasing, cell cycle arrested, alterations of cell migration and invasion behaviors, decreasing phosphorylation level of Akt and GSK-3β in vitro, and significantly suppressing the xenograft tumor growth with decreasing expression of β-catenin, p-GSK3β, and cyclinD1 in vivo. The oncogenic sCLU expression was closely associated with tumor progression, and it should be a novel potential molecular-targeted therapy for HCC.
Part of the book: Hepatocellular Carcinoma