The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells  

作　　者：Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang 

机构地区：[1]State Key Laboratory of New Pharmaceutical Preparations and Excipients/Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science,Chemical Biology Key Laboratory of Hebei Province,Hebei University,Baoding 071002,China [2]CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing 100190,China

出　　处：《Science China(Life Sciences)》2024年第9期1867-1880,共14页中国科学（生命科学英文版）

基　　金：supported by National Natural Science Foundation of China(31971304,21807021);Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038);The central government-guided special funds for local scientific and technological development(226Z2603G);Science and Technology Research Project of Higher Education Institutions in Hebei Province(JZX2023001,ZD2022075);Hebei Youth Top Talent Project.National High-End Foreign Expert Recruitment Plan(G2022003007L);The Research and Innovation Team of Hebei University(IT2023C06,IT2023A01);Natural Science Foundation of Hebei province(B2020201055);Hebei Province Innovation Capability Enhancement Plan Project(22567632H)。

摘　　要：Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of cancer.Currently,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been treated.However,the underlying mechanisms regulating the therapeutic escape remain unknown.To this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the mechanism.Mechanistically,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and metastasis.Notably,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and N-cadherin.The obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关 键 词：therapeutic escape breast cancer stem cells MOTILITY p38/MAPK signaling pathway molecular mechanism 

分 类 号：R737.9[医药卫生—肿瘤]