Li Xiangling, Jiang Shilong, Jiang Ting, Sun Xinyuan, Guan Yidi, Fan Songqing, Cheng Yan
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug, Changsha 410011, China.
Cancers (Basel). 2023 May 26;15(11):2924. doi: 10.3390/cancers15112924.
Breast cancer is the most common deadly malignancy in women worldwide. In particular, triple-negative breast cancer (TNBC) exhibits the worst prognosis among four subtypes of breast cancer due to limited treatment options. Exploring novel therapeutic targets holds promise for developing effective treatments for TNBC. Here, we demonstrated for the first time that LEMD1 (LEM domain containing 1) is highly expressed in TNBC and contributes to reduced survival in TNBC patients, through analysis of both bioinformatic databases and collected patient samples. Furthermore, LEMD1 silencing not only inhibited the proliferation and migration of TNBC cells in vitro, but also abolished tumor formation of TNBC cells in vivo. Knockdown of LEMD1 enhanced the sensitivity of TNBC cells to paclitaxel. Mechanistically, LEMD1 promoted the progress of TNBC by activating the ERK signaling pathway. In summary, our study revealed that LEMD1 may act as a novel oncogene in TNBC, and targeting LEMD1 may be exploited as a promising therapeutic approach to enhance the efficacy of chemotherapy against TNBC.
乳腺癌是全球女性中最常见的致命恶性肿瘤。特别是，三阴性乳腺癌（TNBC）在乳腺癌的四种亚型中预后最差，因为治疗选择有限。探索新的治疗靶点有望为TNBC开发有效的治疗方法。在此，我们通过对生物信息数据库和收集的患者样本进行分析，首次证明LEMD1（含LEM结构域1）在TNBC中高表达，并导致TNBC患者生存率降低。此外，LEMD1沉默不仅在体外抑制TNBC细胞的增殖和迁移，还在体内消除了TNBC细胞的肿瘤形成。敲低LEMD1增强了TNBC细胞对紫杉醇的敏感性。机制上，LEMD1通过激活ERK信号通路促进TNBC的进展。总之，我们的研究表明LEMD1可能是TNBC中的一种新型癌基因，靶向LEMD1可能是一种有前景的治疗方法，可提高化疗对TNBC的疗效。
