盐酸他莫昔芬（Tamoxifen）是治疗雌激素受体阳性（ER +）乳腺癌最有效的工具之一。然而，对他莫昔芬的内在不敏感性和抗药性仍然是实现最佳疗效和治愈疗法的一个重大障碍。在本研究中，我们报告了F-box和富含亮氨酸重复蛋白16（FBXL16）位于ER + 乳腺癌细胞的线粒体中。线粒体中的FBXL16在维持线粒体呼吸作用方面发挥重要作用，从而调节ER + 乳腺癌细胞对他莫昔芬治疗的敏感性。重要的是，高水平的FBXL16表达与ER + 乳腺癌患者的整体生存率较差显著相关。此外，线粒体抑制与FBXL16耗竭在增加ER + 乳腺癌细胞对他莫昔芬治疗的敏感性方面具有相似的表型。综上所述，我们的研究证明了FBXL16作为一种新的调节剂对他莫昔芬敏感性的作用。因此，靶向FBXL16可能成为提高ER + 乳腺癌细胞对他莫昔芬疗效的一种有前景的方法。© 2023. 该作者（们）通过专有许可授予日本人类细胞学会。

Tamoxifen is one of the most effective therapeutic tools for estrogen receptor-positive (ER +) breast cancer. However, the intrinsic insensitivity and resistance to tamoxifen remains a significant hurdle for achieving optimal responses and curative therapy. In this study, we report that F-box and leucine-rich repeat protein 16 (FBXL16) is located in the mitochondria of ER + breast cancer cells. The mitochondrial FBXL16 plays an essential role in sustaining mitochondrial respiration and thereby regulates the sensitivity of ER + breast cancer cells to tamoxifen treatment. Importantly, high FBXL16 expression is significantly correlated with poor overall survival of ER + breast cancer patients. Moreover, mitochondrial inhibition phenocopies FBXL16 depletion in terms of sensitizing the ER + breast cancer cells to tamoxifen treatment. Together, our study demonstrates that FBXL16 acts as a novel regulator of tamoxifen sensitivity. Thus, targeting FBXL16 may serve as a promising approach for improving the therapeutic efficacy of tamoxifen in ER + breast cancer cells.© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.