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Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
Wu, Changjie; Lyu, Junfang; Yang, Eun Ju; Liu, Yifan; Zhang, Baoyuan; Shim, Joong Sup
2018-08-10
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume9
Abstract

ARID1A, a component of the SWI/SNF chromatin remodeling complex, is a tumor suppressor with a high frequency of inactivating mutations in many cancers. Therefore, ARID1A deficiency has been exploited therapeutically for treating cancer. Here we show that ARID1A has a synthetic lethal interaction with aurora kinase A (AURKA) in colorectal cancer (CRC) cells. Pharmacological and genetic perturbations of AURKA selectively inhibit the growth of ARID1A-deficient CRC cells. Mechanistically, ARID1A occupies the AURKA gene promoter and negatively regulates its transcription. Cells lacking ARID1A show enhanced AURKA transcription, which leads to the persistent activation of CDC25C, a key protein for G2/M transition and mitotic entry. Inhibiting AURKA activity in ARID1A-deficient cells significantly increases G2/M arrest and induces cellular multinucleation and apoptosis. This study shows a novel synthetic lethality interaction between ARID1A and AURKA and indicates that pharmacologically inhibiting the AURKA-CDC25C axis represents a novel strategy for treating CRC with ARID1A loss-of-function mutations.

DOI10.1038/s41467-018-05694-4
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000441306700008
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:35   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1 Faculty of Health Sciences, University of Macau, Avenida da Universidade, 999078 Taipa, Macau SAR, China
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Wu, Changjie,Lyu, Junfang,Yang, Eun Ju,et al. Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells[J]. NATURE COMMUNICATIONS,2018,9.
APA Wu, Changjie,Lyu, Junfang,Yang, Eun Ju,Liu, Yifan,Zhang, Baoyuan,&Shim, Joong Sup.(2018).Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells.NATURE COMMUNICATIONS,9.
MLA Wu, Changjie,et al."Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells".NATURE COMMUNICATIONS 9(2018).
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