Loss of GABARAPL1 confers ferroptosis resistance to cancer stem-like cells in hepatocellular carcinoma

被引：24
作者：
Du, Xiaojing [1 ,2 ]
Qi, Zhuoran
Xu, Jinzhi [3 ]
Guo, Mengzhou [3 ]
Zhang, Xingxing [2 ,3 ,4 ]
Yu, Zhijie [2 ,5 ]
Cao, Xin [6 ]
Xia, Jinglin [1 ,2 ,3 ]
机构：
[1] Fudan Univ, Minhang Hosp, Dept Gastroenterol, Shanghai, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Di, Wenzhou 325000, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai, Peoples R China
[4] Anhui Univ Sci & Technol, Affiliated Fengxian Hosp, Shanghai Fengxian Dist Cent Hosp, Dept Gastroenterol, Shanghai, Peoples R China
[5] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou Key Lab Hematol, Wenzhou, Peoples R China
[6] Fudan Univ, Inst Clin Sci, Zhongshan Hosp, Shanghai 200032, Peoples R China
来源：
MOLECULAR ONCOLOGY | 2022年 / 16卷 / 20期
基金：
上海市自然科学基金; 中国国家自然科学基金;
关键词：
cancer stem-like cell; ferroptosis; GABARAPL1; hepatocellular carcinoma; sorafenib;
D O I：
10.1002/1878-0261.13305
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Cancer stem-like cells (CSLC) are considered a major contributor to the development and progression of hepatocellular carcinoma (HCC). Previous studies indicated that CSLC are characterized by resistance to ferroptosis, a type of lipid peroxidation-dependent cell death. Here, we identified a set of ferroptosis-related stemness genes (FRSG) and found that these genes may be involved in immune infiltration in HCC. A four-FRSG (CDKN2A, GABARAPL1, HRAS, RPL8) risk model with prognostic prediction was constructed by a Cox analysis in HCC. Among these four genes, GABARAPL1 was downregulated in HCC tumor-repopulating cells (TRC; a type of CSLC). Its downregulation decreased the sensitivity of HCC TRC to erastin- or sorafenib-triggered ferroptosis. Together, we uncovered a molecular mechanism via which CSLC could achieve tolerance to ferroptosis. Further studies may provide potential therapeutic strategies targeting CSLC in HCC.
引用
收藏
页码：3703 / 3719
页数：17
相关论文
共 36 条
[1]   Lipid storage and lipophagy regulates ferroptosis [J].
Bai, Yuansong ;
Meng, Lingjun ;
Han, Leng ;
Jia, Yuanyuan ;
Zhao, Yanan ;
Gao, Huan ;
Kang, Rui ;
Wang, Xiaofeng ;
Tang, Daolin ;
Dai, Enyong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2019, 508 (04) :997-1003
[2]   Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression [J].
Becht, Etienne ;
Giraldo, Nicolas A. ;
Lacroix, Laetitia ;
Buttard, Benedicte ;
Elarouci, Nabila ;
Petitprez, Florent ;
Selves, Janick ;
Laurent-Puig, Pierre ;
Sautes-Fridman, Catherine ;
Fridman, Wolf H. ;
de Reynies, Aurelien .
GENOME BIOLOGY, 2016, 17
[3]   The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells [J].
Boyer-Guittaut, Michael ;
Poillet, Laura ;
Liang, Qiuli ;
Bole-Richard, Elodie ;
Ouyang, Xiaosen ;
Benavides, Gloria A. ;
Chakrama, Fatima-Zahra ;
Fraichard, Annick ;
Darley-Usmar, Victor M. ;
Despouy, Gilles ;
Jouvenot, Michele ;
Delage-Mourroux, Regis ;
Zhang, Jianhua .
AUTOPHAGY, 2014, 10 (06) :986-1003
[4]   LGR5 marks targetable tumor-initiating cells in mouse liver cancer [J].
Cao, Wanlu ;
Li, Meng ;
Liu, Jiaye ;
Zhang, Shaoshi ;
Noordam, Lisanne ;
Verstegen, Monique M. A. ;
Wang, Ling ;
Ma, Buyun ;
Li, Shan ;
Wang, Wenshi ;
Bolkestein, Michiel ;
Doukas, Michael ;
Chen, Kan ;
Ma, Zhongren ;
Bruno, Marco ;
Sprengers, Dave ;
Kwekkeboom, Jaap ;
van der Laan, Luc J. W. ;
Smits, Ron ;
Peppelenbosch, Maikel P. ;
Pan, Qiuwei .
NATURE COMMUNICATIONS, 2020, 11 (01)
[5]   Inhibition of cancer stem cell like cells by a synthetic retinoid [J].
Chen, Junwei ;
Cao, Xin ;
An, Quanlin ;
Zhang, Yao ;
Li, Ke ;
Yao, Wenting ;
Shi, Fuchun ;
Pan, Yanfang ;
Jia, Qiong ;
Zhou, Wenwen ;
Yang, Fang ;
Wei, Fuxiang ;
Wang, Ning ;
Yu, Biao .
NATURE COMMUNICATIONS, 2018, 9
[6]   Broadening horizons: the role of ferroptosis in cancer [J].
Chen, Xin ;
Kang, Rui ;
Kroemer, Guido ;
Tang, Daolin .
NATURE REVIEWS CLINICAL ONCOLOGY, 2021, 18 (05) :280-296
[7]   Ferroptosis: Cancer Stem Cells Rely on Iron until "to Die for" It [J].
Cosialls, Emma ;
El Hage, Rima ;
Dos Santos, Leila ;
Gong, Chang ;
Mehrpour, Maryam ;
Hamai, Ahmed .
CELLS, 2021, 10 (11)
[8]   Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis [J].
Dixon, Scott J. ;
Patel, Darpan ;
Welsch, Matthew ;
Skouta, Rachid ;
Lee, Eric ;
Hayano, Miki ;
Thomas, Ajit G. ;
Gleason, Caroline ;
Tatonetti, Nicholas ;
Slusher, Barbara S. ;
Stockwell, Brent R. .
ELIFE, 2014, 3
[9]   GSVA: gene set variation analysis for microarray and RNA-Seq data [J].
Haenzelmann, Sonja ;
Castelo, Robert ;
Guinney, Justin .
BMC BIOINFORMATICS, 2013, 14
[10]   The functions of Atg8-family proteins in autophagy and cancer: linked or unrelated? [J].
Jacquet, Marine ;
Guittaut, Michael ;
Fraichard, Annick ;
Despouy, Gilles .
AUTOPHAGY, 2021, 17 (03) :599-611
1234