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

Wei Yu Chen, Yuan Chin Tsai, Hsiu Lien Yeh, Florent Suau, Kuo Ching Jiang, Ai Ning Shao, Jiaoti Huang, Yen Nien Liu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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-b (TGFb)-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.

Original languageEnglish
Article numbereaam6826
JournalScience Signaling
Volume10
Issue number492
Publication statusPublished - Aug 15 2017

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Epithelial-Mesenchymal Transition
Androgens
Prostatic Neoplasms
Bone
Androgen Receptors
Neoplasm Metastasis
Bone and Bones
Tumors
Proteins
Cells
Bearings (structural)
Therapeutics
Prostate
Transforming Growth Factors
Collagen Type IV
Collagen Type II
Heterografts
Castration
Bone Development
Brain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. / Chen, Wei Yu; Tsai, Yuan Chin; Yeh, Hsiu Lien; Suau, Florent; Jiang, Kuo Ching; Shao, Ai Ning; Huang, Jiaoti; Liu, Yen Nien.

In: Science Signaling, Vol. 10, No. 492, eaam6826, 15.08.2017.

Research output: Contribution to journalArticle

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AU - Suau, Florent

AU - Jiang, Kuo Ching

AU - Shao, Ai Ning

AU - Huang, Jiaoti

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