TARBP2-enhanced resistance during tamoxifen treatment in breast cancer

Ming Yang Wang, Hsin Yi Huang, Yao Lung Kuo, Chiao Lo, Hung Yu Sun, Yu Jhen Lyu, Bo Rong Chen, Jie Ning Li, Pai Sheng Chen

研究成果: Article同行評審

8 引文 斯高帕斯(Scopus)

摘要

Tamoxifen is the most widely used hormone therapy in estrogen receptor-positive (ER+) breast cancer, which accounts for approximately 70% of all breast cancers. Although patients who receive tamoxifen therapy benefit with respect to an improved overall prognosis, resistance and cancer recurrence still occur and remain important clinical challenges. A recent study identified TAR (HIV-1) RNA binding protein 2 (TARBP2) as an oncogene that promotes breast cancer metastasis. In this study, we showed that TARBP2 is overexpressed in hormone therapy-resistant cells and breast cancer tissues, where it enhances tamoxifen resistance. Tamoxifen-induced TARBP2 expression results in the desensitization of ER+ breast cancer cells. Mechanistically, tamoxifen post-transcriptionally stabilizes TARBP2 protein through the downregulation of Merlin, a TARBP2-interacting protein known to enhance its proteasomal degradation. Tamoxifen-induced TARBP2 further stabilizes SOX2 protein to enhance desensitization of breast cancer cells to tamoxifen, while similar to TARBP2, its induction in cancer cells was also observed in metastatic tumor cells. Our results indicate that the TARBP2-SOX2 pathway is upregulated by tamoxifen-mediated Merlin downregulation, which subsequently induces tamoxifen resistance in ER+ breast cancer.

原文English
文章編號210
期刊Cancers
11
發行號2
DOIs
出版狀態Published - 2019 2月

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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