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Article: Genome-wide CRISPR-Cas9 knockout library screening identified PTPMT1 in cardiolipin synthesis is crucial to survival in hypoxia in liver cancer

TitleGenome-wide CRISPR-Cas9 knockout library screening identified PTPMT1 in cardiolipin synthesis is crucial to survival in hypoxia in liver cancer
Authors
Keywordshypoxia
CRISPR library screening
liver cancer
metabolism
mitochondria
Issue Date2021
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2021, v. 34 n. 4, p. article no. 108676 How to Cite?
AbstractHypoxia, low oxygen (O2), is a key feature of all solid cancers, including hepatocellular carcinoma (HCC). Genome-wide CRISPR-Cas9 knockout library screening is used to identify reliable therapeutic targets responsible for hypoxic survival in HCC. We find that protein-tyrosine phosphatase mitochondrial 1 (PTPMT1), an important enzyme for cardiolipin (CL) synthesis, is the most significant gene and ranks just after hypoxia-inducible factor (HIF)-1α and HIF-1β as crucial to hypoxic survival. CL constitutes the mitochondrial membrane and ensures the proper assembly of electron transport chain (ETC) complexes for efficient electron transfer in respiration. ETC becomes highly unstable during hypoxia. Knockout of PTPMT1 stops the maturation of CL and impairs the assembly of ETC complexes, leading to further electron leakage and ROS accumulation at ETC in hypoxia. Excitingly, HCC cells, especially under hypoxic conditions, show great sensitivity toward PTPMT1 inhibitor alexidine dihydrochloride (AD). This study unravels the protective roles of PTPMT1 in hypoxic survival and cancer development.
Persistent Identifierhttp://hdl.handle.net/10722/304619
ISSN
2023 Impact Factor: 7.5
2023 SCImago Journal Rankings: 4.279
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBao, MHR-
dc.contributor.authorYang, C-
dc.contributor.authorTse, APW-
dc.contributor.authorWei, L-
dc.contributor.authorLee, D-
dc.contributor.authorZhang, MS-
dc.contributor.authorGoh, CC-
dc.contributor.authorChiu, DKC-
dc.contributor.authorYuen, WH-
dc.contributor.authorLaw, CT-
dc.contributor.authorChin, WC-
dc.contributor.authorChui, NNQ-
dc.contributor.authorWong, BPY-
dc.contributor.authorChan, CYK-
dc.contributor.authorNg, IOL-
dc.contributor.authorChung, CYS-
dc.contributor.authorWong, CM-
dc.contributor.authorWong, CCL-
dc.date.accessioned2021-10-05T02:32:44Z-
dc.date.available2021-10-05T02:32:44Z-
dc.date.issued2021-
dc.identifier.citationCell Reports, 2021, v. 34 n. 4, p. article no. 108676-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/304619-
dc.description.abstractHypoxia, low oxygen (O2), is a key feature of all solid cancers, including hepatocellular carcinoma (HCC). Genome-wide CRISPR-Cas9 knockout library screening is used to identify reliable therapeutic targets responsible for hypoxic survival in HCC. We find that protein-tyrosine phosphatase mitochondrial 1 (PTPMT1), an important enzyme for cardiolipin (CL) synthesis, is the most significant gene and ranks just after hypoxia-inducible factor (HIF)-1α and HIF-1β as crucial to hypoxic survival. CL constitutes the mitochondrial membrane and ensures the proper assembly of electron transport chain (ETC) complexes for efficient electron transfer in respiration. ETC becomes highly unstable during hypoxia. Knockout of PTPMT1 stops the maturation of CL and impairs the assembly of ETC complexes, leading to further electron leakage and ROS accumulation at ETC in hypoxia. Excitingly, HCC cells, especially under hypoxic conditions, show great sensitivity toward PTPMT1 inhibitor alexidine dihydrochloride (AD). This study unravels the protective roles of PTPMT1 in hypoxic survival and cancer development.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjecthypoxia-
dc.subjectCRISPR library screening-
dc.subjectliver cancer-
dc.subjectmetabolism-
dc.subjectmitochondria-
dc.titleGenome-wide CRISPR-Cas9 knockout library screening identified PTPMT1 in cardiolipin synthesis is crucial to survival in hypoxia in liver cancer-
dc.typeArticle-
dc.identifier.emailBao, MHR: macus@connect.hku.hk-
dc.identifier.emailYang, C: cxyang@hku.hk-
dc.identifier.emailTse, APW: akipwtse@hku.hk-
dc.identifier.emailLee, D: leederek@hku.hk-
dc.identifier.emailZhang, MS: mistyzs@hku.hk-
dc.identifier.emailLaw, CT: ctlawaa@connect.hku.hk-
dc.identifier.emailChin, WC: doncwc01@hku.hk-
dc.identifier.emailChan, CYK: ykchanaa@hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailChung, CYS: cyschung@hku.hk-
dc.identifier.emailWong, CM: jcmwong@hku.hk-
dc.identifier.emailWong, CCL: carmencl@pathology.hku.hk-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityChung, CYS=rp02672-
dc.identifier.authorityWong, CM=rp00231-
dc.identifier.authorityWong, CCL=rp01602-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2020.108676-
dc.identifier.pmid33503428-
dc.identifier.scopuseid_2-s2.0-85099829524-
dc.identifier.hkuros325822-
dc.identifier.volume34-
dc.identifier.issue4-
dc.identifier.spagearticle no. 108676-
dc.identifier.epagearticle no. 108676-
dc.identifier.isiWOS:000613631500018-
dc.publisher.placeUnited States-

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