Secretory Clusterin: A Promising Target for Chemoresistance of Hepatocellular Carcinoma.
2020
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Chemoresistance remains the major factor for the limited efficacy of HCC treatment. Thus, exploring the mechanisms underlying drug resistance is of great importance. Secretory clusterin (sCLU), a stress-activated and ATP-independent molecular chaperone, is up-regulated in numerous tumors and correlated with malignant phenotypes. For HCC, the implication of sCLU was previously addressed in the tumor growth, metastasis, as well as the early diagnosis and poor prognosis. Notably, accumulating studies have emphasized its vital roles in drug resistance of HCC. Depletion of sCLU synergistically could enhance sensitivity of HCC cells to a variety of chemotherapy agents. Herein, we summarized the potential mechanisms accounting for the sCLU-induced chemoresistance, including promoting apoptosis evasion, facilitating epithelial-mesenchymal transition (EMT), maintaining viability of cancer stem cell (CSC), enhancing drug efflux capacity, and regulating autophagic activities. The current evidences suggest that targeting sCLU might be a promising approach in overcoming chemoresistance of HCC.
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