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

页码：3703 / 3719

页数：17

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