Challenge and Promise: Roles for Clusterin in Pathogenesis, Progression and Therapy of Cancer

Cell Death Differ. 2006 Jan;13(1):12-9. doi: 10.1038/sj.cdd.4401779.

Abstract

Clusterin (CLU) has been implicated in various cell functions involved in carcinogenesis and tumour progression. There are two known CLU protein isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is proapoptotic, and a secretory form (sCLU) is prosurvival. CLU expression has been associated with tumorigenesis of various malignancies, including tumours of prostate, colon, and breast. Furthermore, CLU expression is modulated by many factors that are believed to regulate tumour growth and/or apoptosis, including 1,25-dihydroxyvitamin D3, transforming growth factor beta-1, ultraviolet radiation, and IR. sCLU upregulation appears to be a general molecular stress response. Presently, preliminary results indicate that therapeutic modalities targeting CLU may be effective in cancer treatment. However, such strategies should make sure that nCLU is not eliminated or reduced. This review summarizes our present understanding of the importance of CLU in various physiological functions including tumour growth, and discusses its relevance to future cancer therapy.

Publication types

  • Review

MeSH terms

  • Apoptosis / physiology
  • Biomarkers, Tumor / genetics
  • Cell Cycle / physiology
  • Clusterin / genetics
  • Clusterin / physiology*
  • DNA Repair
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Neoplasms / physiopathology
  • Neoplasms / therapy
  • Prognosis
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology

Substances

  • Biomarkers, Tumor
  • CLU protein, human
  • Clusterin
  • Protein Isoforms