典型文献
Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer
文献摘要：
Chemoresistance remains a major obstacle to successful treatment of triple negative breast cancer(TNBC).Identification of druggable vulnerabilities is an important aim for TNBC therapy.Here,we report that SERCA2 expression correlates with TNBC progression in human patients,which promotes TNBC cell proliferation,migration and chemoresistance.Mechanistically,SERCA2 interacts with LC3B via LIR motif,facilitating WIPI2-independent autophagosome formation to induce autophagy.Autophagy-mediated SERCA2 degradation induces SERCA2 transactivation through a Ca2+/CaMKK/CREB-1 feedback.Moreover,we found that SERCA2-targeting small molecule RL71 enhances SER-CA2-LC3B interaction and induces excessive autophagic cell death.The increase in SERCA2 expres-sion predisposes TNBC cells to RL71-induced autophagic cell death in vitro and in vivo.This study elucidates a mechanism by which TNBC cells maintain their high autophagy activity to induce chemore-sistance,and suggests increased SERCA2 expression as a druggable vulnerability for TNBC.
文献关键词：
中图分类号：
作者姓名：
Minmin Fan;Jian Gao;Lin Zhou;Wenwen Xue;Yixuan Wang;Jingwei Chen;Wuhao Li;Ying Yu;Bo Liu;Yan Shen;Qiang Xu
作者机构：
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing Drum Tower Hospital,School of Life Sciences,Nanjing University,Nanjing 210023,China;The First Clinical Medical College,Nanjing University of Chinese Medicine,Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor,Nanjing 210023,China;State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Collaborative Innovation Center of Biotherapy,Chengdu 610041,China
文献出处：
引用格式：
[1]Minmin Fan;Jian Gao;Lin Zhou;Wenwen Xue;Yixuan Wang;Jingwei Chen;Wuhao Li;Ying Yu;Bo Liu;Yan Shen;Qiang Xu-.Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer)[J].药学学报（英文版）,2022(12):4407-4423
A类：
Chemoresistance,WIPI2,RL71,predisposes,chemore
B类：
Highly,expressed,SERCA2,triggers,tumor,autophagy,druggable,vulnerability,triple,negative,breast,cancer,remains,major,obstacle,successful,treatment,TNBC,Identification,vulnerabilities,important,aim,therapy,Here,we,report,that,expression,correlates,progression,human,patients,which,promotes,proliferation,migration,chemoresistance,Mechanistically,interacts,LC3B,via,LIR,motif,facilitating,independent,autophagosome,formation,Autophagy,mediated,degradation,induces,transactivation,through,Ca2+,CaMKK,CREB,feedback,Moreover,found,targeting,small,molecule,enhances,interaction,excessive,autophagic,death,cells,induced,vitro,vivo,This,study,elucidates,mechanism,by,maintain,their,high,activity,suggests,increased
AB值：
0.527713
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