Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization Journal Article

   

Authors:	Basnet, H.; Tian, L.; Ganesh, K.; Huang, Y. H.; Macalinao, D. G.; Brogi, E.; Finley, L. W.; Massagué, J.
Article Title:	Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization
Abstract:	Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with high sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, metabolically labeling nascent RNA in rare cell populations in situ for purification and sequencing. Flura-seq revealed hundreds of unique, dynamic organ-specific gene signatures depending on the microenvironment in mouse xenograft breast cancer micrometastases. Specifically, the mitochondrial electron transport Complex I, oxidative stress and counteracting antioxidant programs were induced in pulmonary micrometastases, compared to mammary tumors or brain micrometastases. We confirmed lung metastasis-specific increase in oxidative stress and upregulation of antioxidants in clinical samples, thus validating Flura-seq's utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research. © 2019, Basnet et al.
Keywords:	mouse; breast cancer; lung metastasis; brain metastasis; oxidative stress; cancer biology; in situ transcriptomics
Journal Title:	eLife
Volume:	8
ISSN:	2050-084X
Publisher:	eLife Sciences Publications Ltd.
Date Published:	2019-03-26
Start Page:	e43627
Language:	English
DOI:	10.7554/eLife.43627
PUBMED:	30912515
PROVIDER:	scopus
PMCID:	PMC6440742
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064143971&doi=10.7554%2feLife.43627&partnerID=40&md5=62330f06804fcf1cbead0f99cf1bdfbc
Notes:	Article -- Export Date: 1 May 2019 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/145607