Asset Details
Do you wish to reserve the book?
Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
Do you wish to request the book?
Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
2018
Overview
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.
ARID1A is highly inactivated in cancer. Here, the authors show that ARID1A has a synthetic lethal interaction with AURKA in colorectal cancer cells and that ARID1A deficiency activates the AURKA target CDC25C, whose inhibitors also cause cell death in the ARID1A-deficient cell lines.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 38
/ 38/15
/ 38/88
/ 38/89
/ 49
/ 49/98
/ 631/154
/ 631/67
/ 631/92
/ 64
/ 64/60
/ 692/4017
/ Animals
/ Aurora Kinase A - antagonists & inhibitors
/ Aurora Kinase A - metabolism
/ Cancer
/ cdc25 Phosphatases - metabolism
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - pathology
/ Drug Evaluation, Preclinical
/ Female
/ G2 Phase
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Mitosis
/ Mutation
/ Nuclear Proteins - deficiency
/ Nuclear Proteins - metabolism
/ Proteins
/ Science
/ Synthetic Lethal Mutations - genetics
/ Transcription Factors - deficiency
