APA
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Sreekumar, A., Lu, M., Choudhury, B., Pan, T.-chi, Pant, D. K., Sterner, C. J., … Chodosh, L. A. (2023). B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling. BioRxiv. https://doi.org/10.1101/2023.01.31.526529
Chicago/Turabian
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Sreekumar, Amulya, Michelle Lu, Biswa Choudhury, Tien-chi Pan, Dhruv K. Pant, Christopher J. Sterner, George K. Belka, et al. “B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling.” bioRxiv (February 2023).
MLA
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Sreekumar, Amulya, et al. “B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling.” BioRxiv, openRxiv, Feb. 2023, doi:10.1101/2023.01.31.526529.
BibTeX Click to copy
@article{sreekumar2023a,
title = {B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling},
year = {2023},
month = feb,
journal = {bioRxiv},
publisher = {openRxiv},
doi = {10.1101/2023.01.31.526529},
author = {Sreekumar, Amulya and Lu, Michelle and Choudhury, Biswa and Pan, Tien-chi and Pant, Dhruv K. and Sterner, Christopher J. and Belka, George K. and Toriumi, Takashi and Benz, Brian and Escobar-Aguirre, Matias and Marino, Francesco E. and Esko, Jeffrey D. and Chodosh, Lewis A.},
month_numeric = {2}
}
Breast cancer mortality results primarily from incurable recurrent tumors seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling dormant 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 covalently attaches glycosaminoglycans (GAGs) to proteins to generate proteoglycans and its germline loss-of-function causes skeletal dysplasias. We determined that B3GALT6-mediated biosynthesis of the GAG heparan sulfate 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 identify a role for B3GALT6 in cancer and suggest targeting FGF signaling as a novel approach to preventing recurrence by eradicating dormant RTCs.