Open AccessLoss of GABARAPL1 confers ferroptosis resistance to cancer stem‐like cells in hepatocellular carcinoma
Author(s) -
Du Xiaojing,
Qi Zhuoran,
Xu Jinzhi,
Guo Mengzhou,
Zhang Xingxing,
Yu Zhijie,
Cao Xin,
Xia Jinglin
Publication year - 2022
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13305
Subject(s) - hepatocellular carcinoma , cancer research , liver cancer , biology , cancer stem cell , stem cell , cdkn2a , cancer cell , cancer , microbiology and biotechnology , genetics
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.