Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma

Jiaomeng Pan; Mao Zhang; Liangqing Dong; Shuyi Ji; Juan Zhang; Shu Zhang; Youpei Lin; Xiaoying Wang; Zhenbin Ding; Shuangjian Qiu; Daming Gao; Jian Zhou; Jia Fan; Qiang Gao

doi:10.1080/15548627.2022.2117893

Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma

Autophagy. 2023 Apr;19(4):1184-1198. doi: 10.1080/15548627.2022.2117893. Epub 2022 Sep 7.

Authors

Jiaomeng Pan¹, Mao Zhang¹, Liangqing Dong¹, Shuyi Ji², Juan Zhang¹, Shu Zhang¹, Youpei Lin¹, Xiaoying Wang¹, Zhenbin Ding¹, Shuangjian Qiu¹, Daming Gao³, Jian Zhou¹, Jia Fan^{1

4

5}, Qiang Gao^{1

4

5}

Affiliations

¹ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
² Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China.
³ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
⁴ Institute of Biomedical Sciences, Fudan University, Shanghai, China.
⁵ State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.

Abstract

cld-CASP3: cleaved caspase 3; cld-PARP: cleaved PARP; DTP: drug tolerant persister; GO: Gene Ontology; GTEx: The Genotype-Tissue Expression; HCC: hepatocellular carcinoma; HCQ: hydroxychloroquine; IC50: half maximal inhibitory concentration value; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAPTM5: lysosomal protein transmembrane 5; NT: non-targeting; PDC: patient-derived primary cell lines; PDO: patient-derived primary organoid; TCGA: The Cancer Genome Atlas.

Keywords: Autophagy; LAPTM5; drug resistance; lenvatinib; liver cancer; whole-genome CRISPR-Cas9 screen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / pathology
Clustered Regularly Interspaced Short Palindromic Repeats
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Liver Neoplasms* / pathology
Membrane Proteins / genetics
Poly(ADP-ribose) Polymerase Inhibitors

Substances

lenvatinib
Poly(ADP-ribose) Polymerase Inhibitors
LAPTM5 protein, human
Membrane Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81961128025), Research Projects from the Science and Technology Commission of Shanghai Municipality (grants 19XD1420700, 21JC1401200, 21JC1410100), Shanghai Municipal Key Clinical Specialty and the Beijing iGandan Foundation (GDXZ-08-17).