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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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
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| Web link |
https://www.cell.com/cancer-cell/abstract/S1535-6108(23)00399-9
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| Contributor(s) |
Sreekumar A, Pan T, Pant DK |
| Citation(s) |
38065100 |
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| Submission date |
Aug 21, 2023 |
| Last update date |
Apr 01, 2024 |
| Contact name |
Lewis Chodosh |
| E-mail(s) |
chodosh@pennmedicine.upenn.edu
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| Phone |
(215) 898-1321
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| Organization name |
University of Pennsylvania
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| Department |
Cancer Biology
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| Lab |
Chodosh
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| Street address |
421 Curie Blvd
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| City |
Philadelphia |
| State/province |
Pennsylvania |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (60)
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| 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 |
| GSM7720035 |
Her2/Neu mouse model cells,8Hr,Bio5,run5 |
| GSM7720036 |
Her2/Neu mouse model cells,8hr,Bio3,run2 |
| GSM7720037 |
Her2/Neu mouse model cells,8hr,Bio1,run1 |
| GSM7720038 |
Her2/Neu mouse model cells,Day0,Bio2,run3 |
| GSM7720039 |
Her2/Neu mouse model cells,Day0,Bio3,run2 |
| GSM7720040 |
Her2/Neu mouse model cells,Day0,Bio4,run4 |
| GSM7720041 |
Her2/Neu mouse model cells,Day0,Bio5,run5 |
| GSM7720042 |
Her2/Neu mouse model cells,Day14,Bio2,run3 |
| GSM7720043 |
Her2/Neu mouse model cells,Day14,Bio2,run4 |
| GSM7720044 |
Her2/Neu mouse model cells,Day14,Bio4,run4 |
| GSM7720045 |
Her2/Neu mouse model cells,Day14,Bio5,run5 |
| GSM7720046 |
Her2/Neu mouse model cells,Day14,Bio3,run2 |
| GSM7720047 |
Her2/Neu mouse model cells,Day14,plusDox,Bio1,run2 |
| GSM7720048 |
Her2/Neu mouse model cells,Day14,plusDox,Bio3,run2 |
| GSM7720049 |
Her2/Neu mouse model cells,Day14plusDox,Bio2,run3 |
| GSM7720050 |
Her2/Neu mouse model cells,Day14plusDox,Bio4,run4 |
| GSM7720051 |
Her2/Neu mouse model cells,Day14plusDox,Bio5,run5 |
| GSM7720052 |
Her2/Neu mouse model cells,Day1,Bio2,run3 |
| GSM7720053 |
Her2/Neu mouse model cells,Day1,Bio3,run2 |
| GSM7720054 |
Her2/Neu mouse model cells,Day1,Bio4,run4 |
| GSM7720055 |
Her2/Neu mouse model cells,Day1,Bio5,run5 |
| GSM7720056 |
Her2/Neu mouse model cells,Day1,Bio5,run2 |
| GSM7720057 |
Her2/Neu mouse model cells,Day28,Bio2,run3 |
| GSM7720058 |
Her2/Neu mouse model cells,Day28,Bio4,run4 |
| GSM7720059 |
Her2/Neu mouse model cells,Day28,Bio5,run3 |
| GSM7720060 |
Her2/Neu mouse model cells,Day28,Bio5,run5 |
| GSM7720061 |
Her2/Neu mouse model cells,Day28,Bio3,run2 |
| GSM7720062 |
Her2/Neu mouse model cells,Day28,plusDox,Bio3,run2 |
| GSM7720063 |
Her2/Neu mouse model cells,Day28plusDox,Bio2,run3 |
| GSM7720064 |
Her2/Neu mouse model cells,Day28plusDox,Bio4,run4 |
| GSM7720065 |
Her2/Neu mouse model cells,Day28plusDox,Bio5,run5 |
| GSM7720066 |
Her2/Neu mouse model cells,Day3,Bio1,run4 |
| GSM7720067 |
Her2/Neu mouse model cells,Day3,Bio2,run3 |
| GSM7720068 |
Her2/Neu mouse model cells,Day3,Bio3,run2 |
| GSM7720069 |
Her2/Neu mouse model cells,Day3,Bio4,run4 |
| GSM7720070 |
Her2/Neu mouse model cells,Day3,Bio5,run5 |
| GSM7720071 |
Her2/Neu mouse model cells,Day7,Bio2,run3 |
| GSM7720072 |
Her2/Neu mouse model cells,Day7,Bio2,run5 |
| GSM7720073 |
Her2/Neu mouse model cells,Day7,Bio4,run4 |
| GSM7720074 |
Her2/Neu mouse model cells,Day7,Bio5,run5 |
| GSM7720075 |
Her2/Neu mouse model cells,Day7,Bio3,run2 |
| GSM7720076 |
Her2/Neu mouse model cells,Day7,plusDox,Bio3,run2 |
| GSM7720078 |
Her2/Neu mouse model cells,Day7plusDox,Bio2,run3 |
| GSM7720079 |
Her2/Neu mouse model cells,Day7plusDox,Bio3,run5 |
| GSM7720081 |
Her2/Neu mouse model cells,Day7plusDox,Bio4,run4 |
| GSM7720082 |
Her2/Neu mouse model cells,Day7plusDox,Bio5,run5 |
| GSM7720084 |
Her2/Neu mouse model cells,Day0,Bio1,run1 |
| GSM7720085 |
Her2/Neu mouse model cells,Day0,Bio3,run1 |
| GSM7720087 |
Her2/Neu mouse model cells,Day14,Bio1,run1 |
| GSM7720088 |
Her2/Neu mouse model cells,Day14plusDox,Bio1,run1 |
| GSM7720090 |
Her2/Neu mouse model cells,Day1,Bio1,run1 |
| GSM7720091 |
Her2/Neu mouse model cells,Day28,Bio1,run1 |
| GSM7720092 |
Her2/Neu mouse model cells,Day28plusDox,Bio1,run1 |
| GSM7720094 |
Her2/Neu mouse model cells,Day28plusDox,Bio4,run1 |
| GSM7720095 |
Her2/Neu mouse model cells,Day3,Bio1,run1 |
| GSM7720097 |
Her2/Neu mouse model cells,Day7,Bio1,run1 |
| GSM7720098 |
Her2/Neu mouse model cells,Day7plusDox,Bio1,run1 |
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| Relations |
| BioProject |
PRJNA1007589 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241252_RAW.tar |
12.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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