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

Autor: Xiaojing Du, Zhuoran Qi, Jinzhi Xu, Mengzhou Guo, Xingxing Zhang, Zhijie Yu, Xin Cao, Jinglin Xia
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Oncology, Vol 16, Iss 20, Pp 3703-3719 (2022)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13305
Popis: 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.
Databáze: Directory of Open Access Journals
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