Abstract
Exit of quiescent disseminated cancer cells from dormancy is thought to be responsible for metastatic relapse and a better understanding of dormancy could pave the way for novel therapeutic approaches. We used an in vivo model of triple negative breast cancer brain metastasis to identify differences in transcriptional profiles between dormant and proliferating cancer cells in the brain. BGN gene, encoding a small proteoglycan biglycan, was strongly upregulated in dormant cancer cells in vivo. BGN expression was significantly downregulated in patient brain metastases as compared to the matched primary breast tumors and BGN overexpression in cancer cells inhibited their growth in vitro and in vivo. Dormant cancer cells were further characterized by a reduced expression of glycolysis genes in vivo, and inhibition of glycolysis in vitro resulted in a reversible growth arrest reminiscent of dormancy. Our study identified mechanisms that could be targeted to induce/maintain cancer dormancy and thereby prevent metastatic relapse.
| Original language | English |
|---|---|
| Article number | 1191980 |
| Journal | Frontiers in Oncology |
| Volume | 13 |
| DOIs | |
| Publication status | Published - 29 Jun 2023 |
Bibliographical note
Funding Information:This work was funded by The Leeds Anniversary Research Scholarship from the University of Leeds (to AS) and CRUK Centre Leeds funding (to ML). JW was supported by The Brain Tumour Research and Support across Yorkshire grant and the Medical Research Council UK grant MR/S002057/1. TA was supported by The Brain Tumour Charity programme grant 13/192.
Publisher Copyright:
Copyright © 2023 Sunderland, Williams, Andreou, Rippaus, Fife, James, Kartika, Speirs, Carr, Droop and Lorger.
Data Availability Statement
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.The mRNAseq datasets generated for this study can be found in the Gene Expression Omnibus database with the accession code GSE220017. Publicly available data sets analyzed in this study included GSE2034, GSE5327, GSE12276, GSE14017 and GSE43837.
Analysis of publicly available datasets
Raw data from GSE2034, GSE5327, GSE12276, GSE14017 and GSE43837 was extracted and independently normalized using the R package Affy (26). Gene expression data from Varešlija et al. were downloaded from the GitHub repository rpriedig (27). Pre-normalized BGN gene expression data was further normalized to that of POLR2A expression prior to analysis.
Keywords
- biglycan
- brain metastases
- breast cancer
- dormancy
- glycolysis
- YAP
Access to Document
- Sunderland_etal_FO_Biglycan_And_Reduced_VOR
© 2023 Sunderland, Williams, Andreou, Rippaus, Fife, James, Kartika, Speirs, Carr, Droop and Lorger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.