Chen Feng, Wang Lu, Feng Yanrong, Ma Wenxin, Liu Junqin, Bi Qianyao, Song Yao, Gao Rui, Jia Yanhan
Department of Medical Oncology, Ordos Central Hospital, Ordos, China.
Department of Radiation Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Hum Cell. 2023 Nov;36(6):2087-2098. doi: 10.1007/s13577-023-00961-z. Epub 2023 Aug 3.
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.
他莫昔芬是雌激素受体阳性（ER+）乳腺癌最有效的治疗手段之一。然而，其内在的不敏感性和对他莫昔芬的耐药性仍然是实现最佳反应和治愈性治疗的重大障碍。在本研究中，我们报道F-box和富含亮氨酸重复序列蛋白16（FBXL16）定位于ER+乳腺癌细胞的线粒体中。线粒体中的FBXL16在维持线粒体呼吸中起重要作用，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，FBXL16高表达与ER+乳腺癌患者较差的总生存期显著相关。此外，线粒体抑制在使ER+乳腺癌细胞对他莫昔芬治疗敏感方面模拟了FBXL16缺失的表型。总之，我们的研究表明FBXL16是他莫昔芬敏感性的新型调节因子。因此，靶向FBXL16可能是提高他莫昔芬对ER+乳腺癌细胞治疗疗效的一种有前景的方法。
