Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling

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成果类型：

期刊论文

作者：

Li, Zhe;Xu, Zhi-min;Chen, Wei-peng;Du, Xiao-jing;Ou, Chun-xian;...

通讯作者：

Ma, Jun;Liang, Xiao-yu;Liu, ZW;Liang, XY;Sun, WY

作者机构：

[Liang, Xiao-yu; Li, Zhe; Chen, Wei-peng; Ma, Jun; Liang, XY; Xu, Zhi-min; Ou, Chun-xian; Zhang, Chu-qing; Liu, Zhuo-wei; Luo, Zi-kang] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Peoples R China.

[Liang, Xiao-yu; Li, Zhe; Chen, Wei-peng; Ma, Jun; Du, Xiao-jing; Xu, Zhi-min; Ou, Chun-xian; Liang, XY; Zhang, Chu-qing; Luo, Zi-kang] Sun Yat Sen Univ, Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou, Peoples R China.

[Liang, Xiao-yu; Li, Zhe; Ma, Jun; Du, Xiao-jing; Xu, Zhi-min; Ou, Chun-xian; Liang, XY; Zhang, Chu-qing; Luo, Zi-kang] Sun Yat Sen Univ, Canc Ctr, Dept Radiat Oncol, Guangzhou, Peoples R China.

[Sun, Wan-yang; Wang, Rong; He, Rong-Rong; Sun, WY] Jinan Univ, Guangdong Engn Res Ctr Chinese Med & Dis Susceptib, State Key Lab Bioact Mol & Druggabil Assessment, Guangzhou, Peoples R China.

[Wang, Fudi; Ge, Chao-dong] Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou, Peoples R China.

通讯机构：

[Liang, XY ; Ma, J; Liu, ZW ; Liang, XY] S

[Sun, WY ] J

Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Peoples R China.

Sun Yat Sen Univ, Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou, Peoples R China.

Sun Yat Sen Univ, Canc Ctr, Dept Radiat Oncol, Guangzhou, Peoples R China.

语种：

英文

期刊：

Nature Chemical Biology

ISSN：

1552-4450

年：

2024

卷：

期：

页码：

1341-1352

DOI：

10.1038/s41589-024-01612-6

基金类别：

National Natural Science Foundation of China [81930072, 82172870, 82103449, 82125038, 82274403, 82272832]; Key-Area Research and Development Program of Guangdong Province [2019B020230002]; National Natural Science Foundation of China [82073103]; Sun Yat-sen University Cancer Center; Sun Yat-sen University Clinical Research 5010 Program [2019011]; Postdoctoral Innovation Talent Support Program [BX20200396]; China Postdoctoral Science Foundation [2021M693644]; Guangdong Basic and Applied Basic Research Foundation [2023B1515020020]

机构署名：

本校为其他机构

院系归属：

公共卫生学院

摘要：

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer ...

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Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling

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