全基因组 CRISPR 筛选鉴定 LAPTM5 驱动肝癌对仑伐替尼耐药。
Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma.
机构信息
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.
Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China.
出版信息
Autophagy. 2023 Apr;19(4):1184-1198. doi: 10.1080/15548627.2022.2117893. Epub 2022 Sep 7.
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.
摘要
cld-CASP3：裂解的半胱氨酸天冬氨酸蛋白酶 3；cld-PARP：裂解的多聚（ADP-核糖）聚合酶；DTP：耐药持久细胞；GO：基因本体论；GTEx：基因型-组织表达；HCC：肝细胞癌；HCQ：羟氯喹；IC50：半最大抑制浓度值；KEGG：京都基因与基因组百科全书；LAPTM5：溶酶体蛋白跨膜 5；NT：非靶向；PDC：患者来源的原代细胞系；PDO：患者来源的原代类器官；TCGA：癌症基因组图谱。
相似文献
1
Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma.全基因组 CRISPR 筛选鉴定 LAPTM5 驱动肝癌对仑伐替尼耐药。
Autophagy. 2023 Apr;19(4):1184-1198. doi: 10.1080/15548627.2022.2117893. Epub 2022 Sep 7.
2
Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma.基于全基因组 CRISPR 激活筛选鉴定出 LRP8 在肝癌索拉非尼耐药中的作用。
Biochem Biophys Res Commun. 2020 Jun 11;526(4):1170-1176. doi: 10.1016/j.bbrc.2020.04.040. Epub 2020 Apr 18.
3
GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma modulation of lysosomal functions.GNS561，一种临床阶段的 PPT1 抑制剂，对肝癌有效，能调节溶酶体功能。
Autophagy. 2022 Mar;18(3):678-694. doi: 10.1080/15548627.2021.1988357. Epub 2021 Nov 5.
4
Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma.全基因组 CRISPR 筛选揭示 SGOL1 是索拉非尼治疗的肝细胞癌的可用药靶标。
Lab Invest. 2018 Jun;98(6):734-744. doi: 10.1038/s41374-018-0027-6. Epub 2018 Feb 21.
5
Targeting PARP and autophagy evoked synergistic lethality in hepatocellular carcinoma.靶向 PARP 和自噬可在肝癌中引发协同致死作用。
Carcinogenesis. 2020 May 14;41(3):345-357. doi: 10.1093/carcin/bgz104.
6
Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.全基因组 CRISPR 筛选鉴定出肝癌中 DOCK1 抑制与二甲双胍的合成致死性。
Protein Cell. 2022 Nov;13(11):825-841. doi: 10.1007/s13238-022-00906-6. Epub 2022 Feb 26.
7
Genome-wide CRISPR knockout screens identify ADAMTSL3 and PTEN genes as suppressors of HCC proliferation and metastasis, respectively.全基因组 CRISPR 敲除筛选鉴定出 ADAMTSL3 和 PTEN 基因分别为 HCC 增殖和转移的抑制基因。
J Cancer Res Clin Oncol. 2020 Jun;146(6):1509-1521. doi: 10.1007/s00432-020-03207-9. Epub 2020 Apr 7.
8
Strategies for HCC target discovery.肝癌靶点发现策略。
Aging (Albany NY). 2017 Apr;9(4):1088-1089. doi: 10.18632/aging.101233.
9
Genome-Wide CRISPR/Cas9 Library Screening Identified that DUSP4 Deficiency Induces Lenvatinib Resistance in Hepatocellular Carcinoma.全基因组 CRISPR/Cas9 文库筛选发现 DUSP4 缺失诱导肝癌对仑伐替尼耐药。
Int J Biol Sci. 2022 Jul 4;18(11):4357-4371. doi: 10.7150/ijbs.69969. eCollection 2022.
10
CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma.成年小鼠肝脏的CRISPR/Cas9基因编辑表明，Dnajb1-Prkaca基因融合足以诱发类似纤维板层型肝细胞癌的肿瘤。
Gastroenterology. 2017 Dec;153(6):1662-1673.e10. doi: 10.1053/j.gastro.2017.09.008. Epub 2017 Sep 18.
引用本文的文献
1
WDFY4 Promotes the Progression of Atherosclerosis by Regulating Ferroptosis Mediated by the LAPTM5/CDC42/mTOR/4EBP1/SLC7A11 Pathway.WDFY4通过调节由LAPTM5/CDC42/mTOR/4EBP1/SLC7A11途径介导的铁死亡来促进动脉粥样硬化的进展。
J Cell Mol Med. 2025 Aug;29(15):e70729. doi: 10.1111/jcmm.70729.
2
Different inhibitory effect of a neuropilin-1 monoclonal antibody on different types of hepatocellular carcinoma.神经纤毛蛋白-1单克隆抗体对不同类型肝细胞癌的不同抑制作用。
Discov Oncol. 2025 Jul 29;16(1):1437. doi: 10.1007/s12672-025-03149-z.
3
Efficacy of Lenvatinib Versus Sorafenib in the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.仑伐替尼与索拉非尼治疗不可切除肝细胞癌的疗效：一项系统评价和荟萃分析
Asian Pac J Cancer Prev. 2025 Jun 1;26(6):1943-1952. doi: 10.31557/APJCP.2025.26.6.1943.
4
Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.肝细胞癌中的免疫微环境：从发病机制到免疫治疗
Cell Mol Immunol. 2025 Jun 11. doi: 10.1038/s41423-025-01308-4.
5
Biomarker identification associated with M2 tumor-associated macrophage infiltration in glioblastoma.与胶质母细胞瘤中M2肿瘤相关巨噬细胞浸润相关的生物标志物鉴定
Front Neurol. 2025 May 14;16:1545608. doi: 10.3389/fneur.2025.1545608. eCollection 2025.
6
Transcriptomics of Various Diseases Reveals the Core Role of Immune System Pathways in Retinal Damage Repair and Nerve Regeneration.多种疾病的转录组学揭示了免疫系统通路在视网膜损伤修复和神经再生中的核心作用。
Mol Neurobiol. 2025 Apr 17. doi: 10.1007/s12035-025-04929-y.
7
ARL8B regulates lysosomal function and predicts poor prognosis in hepatocellular carcinoma.ARL8B调节溶酶体功能并预示肝细胞癌预后不良。
Sci Rep. 2025 Apr 10;15(1):12278. doi: 10.1038/s41598-025-97616-w.
8
Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine.变革癌症治疗：整合患者来源的类器官和CRISPR筛选以实现精准医学
Front Pharmacol. 2025 Mar 25;16:1563198. doi: 10.3389/fphar.2025.1563198. eCollection 2025.
9
Syntaxin-6 mediated autophagy confers lenvatinib resistance in hepatocellular carcinoma.Syntaxin-6介导的自噬赋予肝细胞癌对乐伐替尼的耐药性。
Oncogene. 2025 Apr 3. doi: 10.1038/s41388-025-03371-7.
10
Genome-wide CRISPR Screening Identifies NFκB and c-MET as Druggable Targets to Sensitize Lenvatinib Treatment in Hepatocellular Carcinoma.全基因组CRISPR筛选确定NFκB和c-MET为可药物靶向，使肝癌对乐伐替尼治疗敏感。
Cell Mol Gastroenterol Hepatol. 2025;19(7):101502. doi: 10.1016/j.jcmgh.2025.101502. Epub 2025 Mar 20.
本文引用的文献
1
Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors.同时抑制 IGF1R 和 ERK 可提高胰腺癌对自噬抑制剂的敏感性。
Cancer Res. 2022 Feb 15;82(4):586-598. doi: 10.1158/0008-5472.CAN-21-1443.
2
Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance.对耐乐伐替尼的肝细胞癌进行全基因组规模的CRISPR-Cas9基因敲除筛选
Cell Death Discov. 2021 Nov 18;7(1):359. doi: 10.1038/s41420-021-00747-y.
3
EGFR activation limits the response of liver cancer to lenvatinib.表皮生长因子受体（EGFR）激活限制了肝癌对乐伐替尼的反应。
Nature. 2021 Jul;595(7869):730-734. doi: 10.1038/s41586-021-03741-7. Epub 2021 Jul 21.
4
IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation.IL-6 通过促进 BECN1 磷酸化来调节自噬和化疗耐药性。
Nat Commun. 2021 Jun 15;12(1):3651. doi: 10.1038/s41467-021-23923-1.
5
Lenvatinib Targets FGF Receptor 4 to Enhance Antitumor Immune Response of Anti-Programmed Cell Death-1 in HCC.乐伐替尼靶向成纤维细胞生长因子受体4以增强抗程序性细胞死亡蛋白1在肝癌中的抗肿瘤免疫反应。
Hepatology. 2021 Nov;74(5):2544-2560. doi: 10.1002/hep.31921. Epub 2021 Aug 25.
6
ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma.ADAMTSL5是肝细胞癌肿瘤发生和耐药性背后的一个表观遗传激活基因。
J Hepatol. 2021 Apr;74(4):893-906. doi: 10.1016/j.jhep.2020.11.008. Epub 2020 Nov 13.
7
HGF protected against diabetic nephropathy via autophagy-lysosome pathway in podocyte by modulating PI3K/Akt-GSK3β-TFEB axis.肝细胞生长因子通过调节PI3K/Akt-GSK3β-TFEB轴，经足细胞自噬-溶酶体途径对糖尿病肾病起到保护作用。
Cell Signal. 2020 Nov;75:109744. doi: 10.1016/j.cellsig.2020.109744. Epub 2020 Aug 19.
8
Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression.HGF/c-MET 轴的激活促进了高 c-MET 表达的肝癌细胞对乐伐替尼的耐药性。
Med Oncol. 2020 Mar 12;37(4):24. doi: 10.1007/s12032-020-01350-4.
9
mRECIST for HCC: Performance and novel refinements.肝癌的改良RECIST标准：性能与新改进
J Hepatol. 2020 Feb;72(2):288-306. doi: 10.1016/j.jhep.2019.09.026.
10
miR-541 potentiates the response of human hepatocellular carcinoma to sorafenib treatment by inhibiting autophagy.miR-541 通过抑制自噬增强人肝癌细胞对索拉非尼治疗的反应。
Gut. 2020 Jul;69(7):1309-1321. doi: 10.1136/gutjnl-2019-318830. Epub 2019 Nov 14.
Zotero 插件