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

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

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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.

therapeutic escapebreast cancer stem cellsmotilityp38/MAPK signaling pathwaymolecular mechanism

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

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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

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing 100190,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaScience Fund for Creative Research Groups of Nature Science Foundation of Hebei Provincecentral governmentguided special funds for local scientific and technological developmentScience and Technology Research Project of Higher Education Institutions in Hebei ProvinceScience and Technology Research Project of Higher Education Institutions in Hebei ProvinceHebei Youth Top Talent ProjectNational High-End Foreign Expert Recruitment PlanResearch and Innovation Team of Hebei UniversityResearch and Innovation Team of Hebei UniversityNatural Science Foundation of Hebei provinceHebei Province Innovation Capability Enhancement Plan Project

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2024

10.1007/s11427-023-2585-5

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(9)