FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway  

作　　者：Guanglei Chen Lisha Sun Xi Gu Liping Ai Jie Yang Zhan Zhang Pengjie Hou Yining Wang Xunyan Ou Xiaofan Jiang Xinbo Qiao Qingtian Ma Nan Niu Jinqi Xue Hao Zhang Yongliang Yang Caigang Liu 

机构地区：[1]Department of Oncology,Cancer Stem Cell and Translation Medicine Lab,Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province,Shengjing Hospital of China Medical University,Shenyang 110004,China [2]School of Bioengineering,Dalian University of Technology,Dalian 116024,China

出　　处：《Science China(Life Sciences)》2023年第12期2805-2817,共13页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (82203804,81872159);345 Talent Project of Shengjing Hospital of China Medical University。

摘　　要：CDK4/6 inhibitors are routinely recommended agents for the treatment of advanced HR+HER2-breast cancer.However,their therapeutic effectiveness in triple-negative breast cancer(TNBC)remains controversial.Here,we observed that the expression level of fibrous sheath interacting protein 1(FSIP1)could predict the treatment response of TNBC to CDK4/6 inhibitors.High FSIP1 expression level was related to a poor prognosis in TNBC,which was associated with the ability of FSIP1 to promote tumor cell proliferation.FSIP1 downregulation led to slowed tumor growth and reduced lung metastasis in TNBC.FSIP1knockout caused cell cycle arrest at the G0/G1 phase and reduced treatment sensitivity to CDK4/6 inhibitors by inactivating the Nanog/CCND1/CDK4/6 pathway.FSIP1 could form a complex with Nanog,protecting it from ubiquitination and degradation,which may facilitate the rapid cell cycle transition from G0/G1 to S phase and exhibit enhanced sensitivity to CDK4/6 inhibitors.Our findings suggest that TNBC patients with high FSIP1 expression levels may be suitable candidates for CDK4/6 inhibitor treatment.

关 键 词：FSIP1 CDK4/6 inhibitors triple-negative breast cancer 

分 类 号：R730.5[医药卫生—肿瘤]