Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing.

Nature Cell Biology
Ryan T DavisDevon A Lawson

Abstract

Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here, we establish a robust method for the identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA sequencing and patient-derived-xenograft models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity but micrometastases harbour a distinct transcriptome program conserved across patient-derived-xenograft models that is highly predictive of poor survival of patients. Pathway analysis revealed mitochondrial oxidative phosphorylation as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of oxidative phosphorylation dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of oxidative phosphorylation in metastasis and highlights its potential as a therapeutic target to prevent metastatic spread in patients with breast cancer.

References

Jan 6, 1999·Biophysical Journal·R C Scaduto, L W Grotyohann
Jul 29, 2000·Leukemia·E M CreaghT G Cotter
Aug 2, 2005·Nature Reviews. Cancer·Britta WeigeltLaura J van 't Veer
Nov 6, 2007·Biophysical Journal·Michelle A DigmanEnrico Gratton
Feb 9, 2008·Cell Death and Differentiation·E GiannoniP Chiarugi
Sep 11, 2008·Journal of Cellular Physiology·Frédéric DayanNathalie M Mazure
Sep 16, 2008·Free Radical Biology & Medicine·Jacek Zielonka, B Kalyanaraman
Apr 22, 2011·Nature Reviews. Cancer·Willem H KoppenolChi V Dang
Aug 2, 2011·Gynecologic Oncology·Michael BodmerChristoph R Meier
Aug 1, 2012·Breast Cancer Research and Treatment·Nananda F ColRowan T Chlebowski
Jan 5, 2014·Nature Protocols·Simone PicelliRickard Sandberg
Mar 13, 2014·Cell Stem Cell·Thordur OskarssonJoan Massagué
Jun 14, 2014·Science·Anoop P PatelBradley E Bernstein
Jul 30, 2014·Cell Reports·Paolo E PorporatoPierre Sonveaux
Nov 21, 2014·Handbook of Clinical Neurology·Paul Fernyhough, Jonathan McGavock
Mar 22, 2015·Molecular & Cellular Proteomics : MCP·Xiaojing LiuJason W Locasale
Apr 14, 2015·Nature Biotechnology·Rahul SatijaAviv Regev
Dec 25, 2015·The Biochemical Journal·Mariana F RodriguesNivea D Amoêdo
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Oct 19, 2016·Nature Reviews. Clinical Oncology·Giampaolo BianchiniLuca Gianni
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The Gene Ontology Consortium
Feb 19, 2017·Molecular Cell·Christoph ZiegenhainWolfgang Enard

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Citations

Jun 27, 2020·Nature Cell Biology·Daniel Haensel, Anthony E Oro
Sep 17, 2020·Cells·Niccolo' RodaMarco Giorgio
Aug 11, 2020·Cancer Metastasis Reviews·Robert ClarkeYue Wang
Sep 22, 2020·Computational and Mathematical Methods in Medicine·Feng QueWei Wang
Nov 27, 2020·British Journal of Cancer·Luke BoulterValerie G Brunton
Jan 5, 2021·Medical Oncology·Jamal Majidpoor, Keywan Mortezaee
Jan 20, 2021·Nature Reviews. Cancer·Gabriele Bergers, Sarah-Maria Fendt
Dec 11, 2020·Journal of Mammary Gland Biology and Neoplasia·Mokryun BaekGloria V Echeverria
Mar 7, 2021·Clinical & Experimental Metastasis·Narmeen S RashidJ Chuck Harrell
Mar 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yijie ZhangWei Xiong
Oct 28, 2020·Journal of Mammary Gland Biology and Neoplasia·Emma D WrennKevin J Cheung
May 27, 2020·Trends in Cancer·Jordan O'MalleyDhyan Chandra
Mar 20, 2021·Seminars in Cancer Biology·Rui ZhangSuling Liu
Mar 12, 2021·Biophysical Journal·Yusheng WuCynthia A Reinhart-King
Oct 1, 2020·Molecular Therapy Oncolytics·Jameson T L BerryBernardo A Mainou
Mar 30, 2021·Frontiers in Oncology·Kevin Roarty, Gloria V Echeverria
Apr 4, 2021·Cancer Discovery·Joan Massagué, Karuna Ganesh
Oct 27, 2020·Journal of Medicinal Chemistry·Yibin XuNouri Neamati
Feb 28, 2021·Annual Review of Immunology·Xianwen RenZemin Zhang
Apr 30, 2021·Cell Metabolism·Matthew R ZanotelliCynthia A Reinhart-King
May 1, 2021·Experimental Hematology & Oncology·Chao Wang, Daya Luo
Jun 3, 2021·Clinical & Experimental Metastasis·Jenna A MosierCynthia A Reinhart-King
May 25, 2021·Molecular Therapy Oncolytics·Guangshun SunYangbai Sun
Jun 11, 2021·Journal of Hematology & Oncology·Yalan LeiSi Shi
Jul 26, 2021·Trends in Cancer·Arianna Giacobbe, Cory Abate-Shen
Jul 22, 2021·The Journal of Experimental Medicine·Roberto VendraminEleonora Leucci
Jul 1, 2021·American Journal of Physiology. Cell Physiology·Kevin M TurnerJun-Lin Guan
Sep 3, 2021·Briefings in Bioinformatics·Mohammad Reza KarimiUlf Schmitz
Oct 2, 2021·Frontiers in Cell and Developmental Biology·Chunlei GuoHui Wang
Oct 9, 2021·British Journal of Cancer·Sarah K Herzog, Suzanne A W Fuqua
Oct 9, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ozge SaatciOzgur Sahin

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Methods Mentioned

BETA
Smartseq2
flow cytometry
scRNA-seq
PCR
environmental stress
xenograft
flow
reverse-transcription PCR
metabolomics profiling
FACS

Software Mentioned

Smartseq2
R package ‘ mixOmics ’
KM Plotter
MeanVarPlot
Enrichr
Seurat analysis
bowtie2
FindAllMarkers
Bowtie
RSEM

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