Targeted Intervention of NF2-YAP Signaling Axis in CD24-Overexpressing Cells Contributes to Encouraging Therapeutic Effects in TNBC

作者全名："Hou, Lingmi; Pu, Lulan; Chen, Yu; Bai, Yuting; Zhou, Yuqing; Chen, Maoshan; Wang, Shuqi; Lv, Yipin; Ma, Cui; Cheng, Panke; Zhang, Kaijiong; Liang, Qi; Deng, Shishan; Wang, Dongsheng"

作者地址："[Zhang, Kaijiong; Wang, Dongsheng] Univ Elect Sci & Technol, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Sch Med,Dept Clin Lab, Chengdu 610041, Sichuan, Peoples R China; [Hou, Lingmi; Pu, Lulan; Chen, Yu; Bai, Yuting; Zhou, Yuqing; Liang, Qi; Deng, Shishan] North Sichuan Med Coll, Affiliated Hosp, Biol Targeting Lab Breast Canc Breast & Thyroid S, Dept Acad Expert Workstn, Nanchong 637000, Sichuan, Peoples R China; [Pu, Lulan; Chen, Yu; Zhou, Yuqing; Deng, Shishan] North Sichuan Med Coll, Dept Anat, Nanchong 637000, Sichuan, Peoples R China; [Bai, Yuting; Wang, Shuqi; Liang, Qi] North Sichuan Med Coll, Affiliated Hosp, Dept Lab Med, Nanchong 637000, Sichuan, Peoples R China; [Hou, Lingmi] Sichuan Univ, West China Hosp, Yingshan Hosp, Dept Breast & Thyroid Surg, Nanchong 673000, Sichuan, Peoples R China; [Chen, Maoshan] Chongqing Med Univ, Affiliated Suining Cent Hosp, Dept Breast & Thyroid Surg, Suining 629000, Sichuan, Peoples R China; [Lv, Yipin] Western Theater Command, Gen Hosp, Dept Digest Dis, Chengdu 610036, Sichuan, Peoples R China; [Ma, Cui] Army Med Univ, Dept Math, Chongqing 400038, Peoples R China; [Cheng, Panke] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Cardiol, Chengdu 610072, Sichuan, Peoples R China"

通信作者："Wang, DS (通讯作者)，Univ Elect Sci & Technol, Sichuan Canc Hosp & Inst, Sichuan Canc Ctr, Sch Med,Dept Clin Lab, Chengdu 610041, Sichuan, Peoples R China.; Liang, Q; Deng, SS (通讯作者)，North Sichuan Med Coll, Affiliated Hosp, Biol Targeting Lab Breast Canc Breast & Thyroid S, Dept Acad Expert Workstn, Nanchong 637000, Sichuan, Peoples R China.; Deng, SS (通讯作者)，North Sichuan Med Coll, Dept Anat, Nanchong 637000, Sichuan, Peoples R China.; Liang, Q (通讯作者)，North Sichuan Med Coll, Affiliated Hosp, Dept Lab Med, Nanchong 637000, Sichuan, Peoples R China."

来源：ACS NANO

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000813207000001

JCR分区：Q1

影响因子：17.1

年份：2022

卷号：16

期号：4

开始页：5807

结束页：5819

文献类型：Article

关键词：triple-negative breast cancer; ferroptosis; tumor-associated macrophages; CD24; NF2; YAP

摘要："Triple-negative breast cancer (TNBC) cells have not been usefully classified, and no targeted therapeutic plans are currently available, resulting in a high recurrence rate and metastasis potential. In this research, CD24(high) cells accounted for the vast majority of TNBC cells, and they were insensitive to Taxol but sensitive to ferroptosis agonists and effectively escaped phagocytosis by tumor-associated macrophages. Furthermore, the NF2-YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24(high) cells, with subsequent ferroptotic regulation and macrophage phagocytosis. In addition, a precision targeted therapy system was designed based on the pH level and glutathione response, and it can be effectively used to target CD24(high) cells to induce lysosomal escape and drug burst release through CO2 production, resulting in enhanced ferroptosis and macrophage phagocytosis through FSP1 and CD24 inhibition mediated by the NF2-YAP signaling axis. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting TNBC tumor growth, with some tumors even disappearing. The composite nanoprecision treatment system reported in this paper is a potential strategic tool for future use in the treatment of TNBC."

基金机构："Foundation of Nanchong Municipal University Cooperative Research and Innovation Team Construction Project [20SXCXTD0001, 19SXHZ0442]; Foundation of the TCM Basic Project of Sichuan TCM Administration [2020JC0055]; Foundation of the Project of Chengdu Science and Technology [2021-YF05-01792-SN]; Sichuan Science and Technology Program [2022YFS0006]; National Natural Science Foundation of China [82000530]"

基金资助正文："This work was funded by the Foundation of Nanchong Municipal University Cooperative Research and Innovation Team Construction Project (No. 20SXCXTD0001, No. 19SXHZ0442), Foundation of the TCM Basic Project of Sichuan TCM Administration (No. 2020JC0055), Foundation of the Project of Chengdu Science and Technology (No. 2021-YF05-01792-SN), Sichuan Science and Technology Program (No. 2022YFS0006), and National Natural Science Foundation of China (No. 82000530). The authors also thank the Shiyanjia Lab (www.shiyanjia.com) for the materials characterization analysis."