Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer

• DOI: 10.1126/scisignal.aam6826
• Publication Date: 2017-08-15T18:20:23Z
• Authors: Wei-Yu Chen; Yuan-Chin Tsai; Hsiu-Lien Yeh; Florent Suau; Kuo-Ching Jiang; Ai-Ning Shao; Jiaoti Huang; Yen-Nien Liu
• Keywords: TGFBI

Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant cancer after ADT. We identified type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced (TGFBI) as an important factor in epithelial-to-mesenchymal transition (EMT) malignant progression of In cell lines, AR signaling stimulated activity transcription SPDEF, which repressed expression TGFBI ADT, antagonism, or overexpression inhibited SPDEF enhanced proliferation rates cells. Knockdown suppressed migration cultured cells reduced tumor brain bone metastasis xenograft models, extending survival tumor-bearing mice. Analysis tissue samples collected before ADT from same patients showed that nuclear abundance increased production TGFBI. Our findings suggest induction promotes can be caused by dysregulation inhibition signaling.