Skip to main content

Research Repository

Advanced Search

Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature

Taylor, Louisa; Wade, Philippa K.; Johnson, James E. C.; Aldighieri, Macha; Morlando, Sonia; Di Leva, Gianpiero; Kerr, Ian D.; Coyle, Beth

Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature Thumbnail


Louisa Taylor

Philippa K. Wade

James E. C. Johnson

Macha Aldighieri

Sonia Morlando

Gianpiero Di Leva

Associate Professor

Associate Professor


Therapy resistance represents an unmet challenge in the treatment of medulloblastoma. Accordingly, the identification of targets that mark drug-resistant cell populations, or drive the proliferation of resistant cells, may improve treatment strategies. To address this, we undertook a targeted approach focused on the multi-functional transcription factor YB-1. Genetic knockdown of YB-1 in Group 3 medulloblastoma cell lines diminished cell invasion in 3D in vitro assays and increased sensitivity to standard-of-care chemotherapeutic vincristine and anti-cancer agents panobinostat and JQ1. For vincristine, this occurred in part by YB-1-mediated transcriptional regulation of multi-drug resistance gene ABCB1, as determined by chromatin immunoprecipitation. Whole transcriptome sequencing of YB-1 knockdown cells identified a role for YB-1 in the regulation of tumourigenic processes, including lipid metabolism, cell death and survival and MYC and mTOR pathways. Stable cisplatin- and vincristine-tolerant Group 3 and SHH cell lines were generated to identify additional mechanisms driving resistance to standard-of-care medulloblastoma therapy. Next-generation sequencing revealed a vastly different transcriptomic landscape following chronic drug exposure, including a drug-tolerant seven-gene expression signature, common to all sequenced drug-tolerant cell lines, representing therapeutically targetable genes implicated in the acquisition of drug tolerance. Our findings provide significant insight into mechanisms and genes underlying therapy resistance in medulloblastoma.


Taylor, L., Wade, P. K., Johnson, J. E. C., Aldighieri, M., Morlando, S., Di Leva, G., …Coyle, B. (2023). Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature. Cancers, 15(4), Article 1086.

Journal Article Type Article
Acceptance Date Feb 4, 2023
Online Publication Date Feb 8, 2023
Publication Date 2023-02
Deposit Date Feb 14, 2023
Publicly Available Date Feb 15, 2023
Journal Cancers
Electronic ISSN 2072-6694
Publisher MDPI AG
Peer Reviewed Peer Reviewed
Volume 15
Issue 4
Article Number 1086
Keywords medulloblastoma, drug resistance, cancer cell invasion, ABC transporter, YB-1, vincristine, metastasis
Public URL
Publisher URL


You might also like

Downloadable Citations