The Role of Clusterin in Carcinogenesis and its Potential Utility as Therapeutic Target

Abstract

Clusterin is a glycoprotein that has been implicated in many processes, including apoptosis, cell cycle regulation and DNA repair. Since clusterin expression has also been associated with tumorigenesis and the progression of various malignancies including prevalent tumors like prostate, colon, bladder and breast, this protein has been proposed as a good candidate for future treatments. There have been numerous studies conducted in cell lines and xenograft models with successful results that, in general, justify the use of clusterin as a therapeutic target. However, it is still necessary to continue with these studies in order to achieve a better understanding of the role of this protein in carcinogenesis and to determine those specific situations in which its therapeutic use may be more favorable. In this review, we will make a brief description of clusterin structure and genetics, its implication in tumorigenesis and cancer progression and its prognosis utility. Finally, we will analyze the effects of clusterin inhibition in different types of cancer.

Apolipoproteins and cancer

“…88 It may be induced by stress and was identified as a cytoprotective chaperone protein that aids folding of secreted proteins. The three isoforms of APOJ were discovered to participate in pro-and antiapoptotic processes 89 and were abnormally regulated in many severe physiological disturbances including cancer initiation and progression. 90 Combined with other chemotherapeutic agents, antisense compounds targeting APOJ proved successful in clinical trials for the treatment of prostate cancer.…”

Cloning and Tissue Expression of Clusterin in Bufo gargarizans

“…Concerning the mechanism of CLU expression, although it is not so clear currently, but influenced by cytokines, growth factors as well as stress ones such as oxidative stress, heat shock, chemotherapy and radiotherapy [14,17] . According to previous reports, the tolerance to chemotherapy and radiotherapy is closely related with CLU expression in several cancers, and CLU up-regulation has been confirmed in many cancers including prostate, kidney, bladder, breast, head and neck, colon, cervical, pancreatic, lung, melanoma lymphoma [16,18] . Therefore, CLU has been considered as a biomarker for tumour malignancy, and it is believed that improvement of tumour cell sensitivity to chemotherapy and radiotherapy is promising way to control cancer by reducing CLU expression [14,[19][20][21] .…”

“…sCLU is a highly glycosylated multifunctional protein, which is widely expressed in a variety of mammalian tissues and participates in many physiological processes, such as cell cycle regulation, DNA repair, and angiogenesis [15] . Recent studies have shown over-expression of CLU in several cancers, whose blocking enhances tumour cell sensitivity to chemotherapy and radiotherapy, therefore, CLU has become an important therapeutic target for cancer treatment [14,16] .…”

sCLU as prognostic biomarker and therapeutic target in osteosarcoma

“…The cytoprotective chaperone protein clusterin (CLU) is involved in multiple physiological processes associated with carcinogenesis and tumor growth, including apoptotic cell death, cell cycle regulation, DNA repair, cell adhesion, tissue remodeling, lipid transport, membrane recycling, and immune system regulation [3,4]. As the major isoform, secretory apolipoprotein J (s)CLU has been extensively investigated in the context of tumor diagnosis and prognosis owing to its antiapoptotic function.…”