Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer

Shiota, Masaki, Zoubeidi, Amina, Kumano, Masafumi, Beraldi, Eliana, Naito, Seiji, Nelson, Colleen, Sorensen, Poul, & Gleave, Martin (2011) Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer. Molecular Cancer Research, 9(12), pp. 1755-1766.

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Abstract

Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.

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ID Code: 52065
Item Type: Journal Article
DOI: 10.1158/1541-7786.MCR-11-0379
ISSN: 1541-7786
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Jul 2012 06:27
Last Modified: 05 Feb 2015 03:55

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