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Series GSE241252 Query DataSets for GSE241252
Status Public on Jan 01, 2024
Title B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Breast cancer mortality results from incurable recurrent tumors, putatively seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling RTC survival is therefore essential for improving patient outcomes. We derived a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant chemotherapy in patients and is enriched for extracellular matrix-related pathways. In vivo CRISPR-Cas9 screening of dormancy-associated candidate genes identified the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness. B3GALT6 is required for the linkage of glycosaminoglycans (GAGs) to proteins to generate proteoglycans and its germline loss-of-function causes skeletal dysplasias. We determined that B3GALT6-mediated biosynthesis of heparan sulfate GAGs predicts poor patient outcomes, promotes tumor recurrence by enhancing dormant RTC survival in multiple contexts, and does so via a B3GALT6-heparan sulfate/HS6ST1-heparan 6-O-sulfation/FGF1-FGFR2 signaling axis. These findings implicate B3GALT6 in cancer and suggest targeting of FGFR2 signaling as a novel approach to eradicate dormant RTCs, thereby preventing recurrence.
Overall design To investigate the genomic and molecular changes through dormancy and recurrence , we designed an in-vitro time series experiment on an in-house cell line derived from a Her2/neu mouse model
Web link
Contributor(s) Sreekumar A, Pan T, Pant DK
Citation(s) 38065100
Submission date Aug 21, 2023
Last update date Apr 01, 2024
Contact name Lewis Chodosh
Phone (215) 898-1321
Organization name University of Pennsylvania
Department Cancer Biology
Lab Chodosh
Street address 421 Curie Blvd
City Philadelphia
State/province Pennsylvania
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (60)
GSM7720032 Her2/Neu mouse model cells,8Hr,Bio2,run3
GSM7720033 Her2/Neu mouse model cells,8Hr,Bio4,run3
GSM7720034 Her2/Neu mouse model cells,8Hr,Bio4,run4
BioProject PRJNA1007589

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE241252_RAW.tar 12.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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