https://scholars.lib.ntu.edu.tw/handle/123456789/634754
標題: | TARBP2-Enhanced Resistance during Tamoxifen Treatment in Breast Cancer | 作者: | Wang, Ming-Yang Huang, Hsin-Yi Kuo, Yao-Lung Chiao Lo Sun, Hung-Yu Lyu, Yu-Jhen Chen, Bo-Rong Li, Jie-Ning Chen, Pai-Sheng |
關鍵字: | SOX2; TARBP2; hormone therapy; merlin; tamoxifen | 公開日期: | 12-二月-2019 | 卷: | 11 | 期: | 2 | 來源出版物: | Cancers | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/634754 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers11020210 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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