UM  > Faculty of Health Sciences
Synthetic lethality of RB1 and aurora A is driven by stathmin-mediated disruption of microtubule dynamics
Lyu,Junfang; Yang,Eun Ju; Zhang,Baoyuan; Wu,Changjie; Pardeshi,Lakhansing; Shi,Changxiang; Mou,Pui Kei; Liu,Yifan; Tan,Kaeling; Shim,Joong Sup
2020-12-01
Source PublicationNature Communications
ISSN2041-1723
Volume11Issue:1
Abstract

RB1 mutational inactivation is a cancer driver in various types of cancer including lung cancer, making it an important target for therapeutic exploitation. We performed chemical and genetic vulnerability screens in RB1-isogenic lung cancer pair and herein report that aurora kinase A (AURKA) inhibition is synthetic lethal in RB1-deficient lung cancer. Mechanistically, RB1 cells show unbalanced microtubule dynamics through E2F-mediated upregulation of the microtubule destabilizer stathmin and are hypersensitive to agents targeting microtubule stability. Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 cells. This study shows that stathmin-mediated disruption of microtubule dynamics is critical to induce synthetic lethality in RB1-deficient cancer and suggests that upstream factors regulating microtubule dynamics, such as AURKA, can be potential therapeutic targets in RB1-deficient cancer.

DOI10.1038/s41467-020-18872-0
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000581916500019
Scopus ID2-s2.0-85092214878
Fulltext Access
Citation statistics
Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorShim,Joong Sup
AffiliationCancer Centre,Faculty of Health Sciences,University of Macau,Avenida da Universidade,Taipa,Macao
First Author AffilicationCancer Centre
Corresponding Author AffilicationCancer Centre
Recommended Citation
GB/T 7714
Lyu,Junfang,Yang,Eun Ju,Zhang,Baoyuan,et al. Synthetic lethality of RB1 and aurora A is driven by stathmin-mediated disruption of microtubule dynamics[J]. Nature Communications,2020,11(1).
APA Lyu,Junfang,Yang,Eun Ju,Zhang,Baoyuan,Wu,Changjie,Pardeshi,Lakhansing,Shi,Changxiang,Mou,Pui Kei,Liu,Yifan,Tan,Kaeling,&Shim,Joong Sup.(2020).Synthetic lethality of RB1 and aurora A is driven by stathmin-mediated disruption of microtubule dynamics.Nature Communications,11(1).
MLA Lyu,Junfang,et al."Synthetic lethality of RB1 and aurora A is driven by stathmin-mediated disruption of microtubule dynamics".Nature Communications 11.1(2020).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Lyu,Junfang]'s Articles
[Yang,Eun Ju]'s Articles
[Zhang,Baoyuan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Lyu,Junfang]'s Articles
[Yang,Eun Ju]'s Articles
[Zhang,Baoyuan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Lyu,Junfang]'s Articles
[Yang,Eun Ju]'s Articles
[Zhang,Baoyuan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.