Asset Details
Do you wish to reserve the book?
The KIF18A Inhibitor ATX020 Induces Mitotic Arrest and DNA Damage in Chromosomally Instable High-Grade Serous Ovarian 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?
The KIF18A Inhibitor ATX020 Induces Mitotic Arrest and DNA Damage in Chromosomally Instable High-Grade Serous Ovarian Cancer Cells
Do you wish to request the book?
The KIF18A Inhibitor ATX020 Induces Mitotic Arrest and DNA Damage in Chromosomally Instable High-Grade Serous Ovarian 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
The KIF18A Inhibitor ATX020 Induces Mitotic Arrest and DNA Damage in Chromosomally Instable High-Grade Serous Ovarian Cancer Cells
2025
Overview
High-grade serous ovarian cancer (HGSOC) is the most common (~80%) and lethal ovarian cancer subtype in the United States, characterized by TP53 mutations and DNA repair defects causing chromosomal instability (CIN). KIF18A is an essential cytoskeletal motor protein for cell division in CIN+ cancer cells, but it is not necessary for cell division in normal cells. Therefore, KIF18A represents a promising target for therapeutic interventions in CIN+ cancers. We investigated the use of a novel KIF18A inhibitor ATX020, for selectively targeting CIN+ HGSOC cells using growth inhibition assays, invasion assays, immunoassays, cell cycle analysis, and immunofluorescence techniques. Using DepMap and flow cytometry, we classified a panel of HGSOC cell lines based on aneuploidy scores (AS) and ploidy levels and identified a correlation between these classifications and sensitivity against ATX020. ATX020 induced cytotoxicity through mitotic arrest and DNA damage, and reduced tumor growth in HGSOC with high aneuploidy scores (AS). Mechanistically, ATX020 blocks KIF18A’s plus-end movement on spindle fibers, increasing spindle length, resulting in chromosomal mis-segregation, aneuploidy, and DNA damage. Our findings suggest that ATX020 inhibits CIN+ HGSOC cells mainly by inducing mitotic arrest and DNA damage, disrupting KIF18A’s function crucial for mitosis.
Publisher
MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
Subject
/ Animals
/ ATX020
/ Cancer
/ Cell Proliferation - drug effects
/ Chromosomal Instability - drug effects
/ Cystadenocarcinoma, Serous - drug therapy
/ Cystadenocarcinoma, Serous - genetics
/ Cystadenocarcinoma, Serous - pathology
/ DNA
/ Female
/ HGSOC
/ Humans
/ KIF18A
/ Kinesins - antagonists & inhibitors
/ Mitosis
/ Mutation
/ Ovarian Neoplasms - drug therapy
/ Ovarian Neoplasms - genetics
/ Ovarian Neoplasms - pathology
/ Ploidy
/ Software
/ Tumors
