Supplementary Figure 1 from Clusterin Mediates TGF-β–Induced Epithelial–Mesenchymal Transition and Metastasis via Twist1 in Prostate Cancer Cells

Shiota, Masaki; Zardan, Anousheh; Takeuchi, Ario; Kumano, Masafumi; Beraldi, Eliana; Naito, Seiji; Zoubeidi, Amina; Gleave, Martin E.

doi:10.1158/0008-5472.22393533.v1

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Supplementary Figure 1 from Clusterin Mediates TGF-β–Induced Epithelial–Mesenchymal Transition and Metastasis via Twist1 in Prostate Cancer Cells

journal contribution

posted on 2023-03-30, 21:15 authored by Masaki Shiota, Anousheh Zardan, Ario Takeuchi, Masafumi Kumano, Eliana Beraldi, Seiji Naito, Amina Zoubeidi, Martin E. Gleave

PDF file - 90K, Slug and Snail don't affect CLU expression. A. PC-3 cells were transfected with 40 nmol/L of the indicated siRNA. At 72 h after transfection, quantitative RT-PCR was performed using the primers and probes for CLU and GAPDH. Each transcript level from cells transfected with control siRNA was set as 1. Boxes, mean; bars, �s.d. B. PC-3 cells were transfected with 40 nmol/L of the indicated siRNA. At 72 h after transfection, whole-cell extracts were analyzed by SDS-PAGE and western blot analysis with specific antibodies

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ARTICLE ABSTRACT

TGF-β promotes epithelial–mesenchymal transition (EMT) and induces clusterin (CLU) expression, linking these genes to cancer metastasis. CLU is a pleiotropic molecular chaperone that confers survival and proliferative advantage to cancer cells. However, the molecular mechanisms by which TGF-β regulates CLU expression and CLU affects metastasis remain unknown. In this study, we report that the transcription factor Twist1 mediates TGF-β–induced CLU expression. By binding to E-boxes in the distal promoter region of CLU gene, Twist1 regulated basal and TGF-β–induced CLU transcription. In addition, CLU reduction reduced TGF-β induction of the mesenchymal markers, N-cadherin and fibronectin, thereby inhibiting the migratory and invasive properties induced by TGF-β. Targeted inhibition of CLU also suppressed metastasis in an in vivo model. Taken together, our findings indicate that CLU is an important mediator of TGF-β–induced EMT, and suggest that CLU suppression may represent a promising therapeutic option for suppressing prostate cancer metastatic progression. Cancer Res; 72(20); 5261–72. ©2012 AACR.