Crosstalk between epithelialmesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer

Masaki Shiota, Momoe Itsumi, Ario Takeuchi, Kenjiro Imada, Akira Yokomizo, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito

研究成果: ジャーナルへの寄稿学術誌査読

36 被引用数 (Scopus)

抄録

Although invasive and metastatic progression via the epithelial-mesenchymal transition (EMT) and acquisition of resistance to castration are both critical steps in prostate cancer, the molecular mechanism of this interaction remains unclear. In this study, we aimed to elucidate the interaction of signaling between castration resistance and EMT, and to apply this information to the development of a novel therapeutic concept using transforming growth factor-b (TGF-b) inhibitor SB525334 combined with androgen-deprivation therapy against prostate cancer usinganin vivomodel. This study revealedthat anEMTinducer (TGF-b) induced full-length androgen receptor (AR) and AR variant expression. In addition, a highly invasive clone showed augmented full-length AR and AR variant expression as well as acquisition of castration resistance. Conversely, full-length AR and AR as well as Twist1 and mesenchymal molecules variant expression were up-regulated in castration-resistant LNCaP xenograft. Finally, TGF-b inhibitor suppressed Twist1 and AR expression as well as prostate cancer growth combined with castration. Taken together, these results demonstrate that Twist1/AR signaling was augmented in castration resistant as well as mesenchymal-phenotype prostate cancer, indicating the molecular mechanism of mutual and functional crosstalk between EMTand castration resistance, which may play a crucial role in prostate carcinogenesis and progression.

本文言語英語
ページ(範囲)889-900
ページ数12
ジャーナルEndocrine-Related Cancer
22
6
DOI
出版ステータス出版済み - 12月 2015

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 腫瘍学
  • 内分泌学
  • 癌研究

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