Secretory Clusterin: A Promising Target for Chemoresistance of Hepatocellular Carcinoma

Author(s): Jie Zhang, Mengna Wu, Yuqing Xu, Qianqian Song, Wenjie Zheng*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 12 , 2020


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Graphical Abstract:


Abstract:

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Chemoresistance remains the major factor for limited efficacy of the HCC treatment. Thus, exploring the mechanisms underlying drug resistance is of great importance. Secretory clusterin (sCLU), a stressactivated 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 tumor growth, metastasis, as well as early diagnosis and poor prognosis. Notably, accumulating studies have emphasized its vital role in drug resistance of HCC. Depletion of sCLU synergistically could enhance the 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 the viability of cancer stem cell (CSC), enhancing drug efflux capacity, and regulating autophagic activities. The current evidence suggest that targeting sCLU might be a promising approach in overcoming chemoresistance of HCC.

Keywords: Hepatocellular carcinoma, secretory clusterin, drug resistance, molecular target, cancer, sCLU.

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Article Details

VOLUME: 20
ISSUE: 12
Year: 2020
Published on: 23 July, 2020
Page: [1153 - 1165]
Pages: 13
DOI: 10.2174/1389557520666200331072122
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