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

Publication ,  Journal Article
Chen, W-Y; Tsai, Y-C; Yeh, H-L; Suau, F; Jiang, K-C; Shao, A-N; Huang, J; Liu, Y-N
Published in: Sci Signal
August 15, 2017

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

Duke Scholars

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

August 15, 2017

Volume

10

Issue

492

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Signal Transduction
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-ets
  • Prostatic Neoplasms
  • Mice, Nude
  • Mice
  • Male
 

Citation

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Chen, W.-Y., Tsai, Y.-C., Yeh, H.-L., Suau, F., Jiang, K.-C., Shao, A.-N., … Liu, Y.-N. (2017). Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. Sci Signal, 10(492). https://doi.org/10.1126/scisignal.aam6826
Chen, Wei-Yu, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, and Yen-Nien Liu. “Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer.Sci Signal 10, no. 492 (August 15, 2017). https://doi.org/10.1126/scisignal.aam6826.
Chen W-Y, Tsai Y-C, Yeh H-L, Suau F, Jiang K-C, Shao A-N, et al. Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. Sci Signal. 2017 Aug 15;10(492).
Chen, Wei-Yu, et al. “Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer.Sci Signal, vol. 10, no. 492, Aug. 2017. Pubmed, doi:10.1126/scisignal.aam6826.
Chen W-Y, Tsai Y-C, Yeh H-L, Suau F, Jiang K-C, Shao A-N, Huang J, Liu Y-N. Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. Sci Signal. 2017 Aug 15;10(492).

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

August 15, 2017

Volume

10

Issue

492

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Signal Transduction
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-ets
  • Prostatic Neoplasms
  • Mice, Nude
  • Mice
  • Male