Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis

Nicole Kiweler, Catherine Delbrouck, Vitaly I. Pozdeev, Laura Neises, Leticia Soriano-Baguet, Kim Eiden, Feng Xian, Mohaned Benzarti, Lara Haase, Eric Koncina, Maryse Schmoetten, Christian Jaeger, Muhammad Zaeem Noman, Alexei Vazquez, Bassam Janji, Gunnar Dittmar, Dirk Brenner, Elisabeth Letellier and Johannes Meiser ()
Additional contact information
Nicole Kiweler: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Catherine Delbrouck: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Vitaly I. Pozdeev: University of Luxembourg
Laura Neises: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Leticia Soriano-Baguet: Faculty of Science, Technology and Medicine, University of Luxembourg, 2 avenue de Université
Kim Eiden: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Feng Xian: Proteomics of cellular signaling, Department of Infection and Immunity, Luxembourg Institute of Health,1a Rue Thomas Edison
Mohaned Benzarti: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Lara Haase: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health
Eric Koncina: University of Luxembourg
Maryse Schmoetten: University of Luxembourg
Christian Jaeger: University of Luxembourg
Muhammad Zaeem Noman: Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health
Alexei Vazquez: University of Glasgow
Bassam Janji: Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health
Gunnar Dittmar: Faculty of Science, Technology and Medicine, University of Luxembourg, 2 avenue de Université
Dirk Brenner: Experimental & Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health
Elisabeth Letellier: University of Luxembourg
Johannes Meiser: Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Metastasis is the most common cause of death in cancer patients. Canonical drugs target mainly the proliferative capacity of cancer cells, which leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions are still poorly understood. Here we show that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism during cytosolic 1C metabolism impairment. Interestingly, antifolate dependent growth-arrest does not correlate with decreased migration capacity. Therefore, using methotrexate as a tool compound allows us to disentangle proliferation and migration to profile the metabolic phenotype of migrating cells. We observe that increased serine de novo synthesis (SSP) supports mitochondrial serine catabolism and inhibition of SSP using the competitive PHGDH-inhibitor BI-4916 reduces cancer cell migration. Furthermore, we show that sole inhibition of mitochondrial serine catabolism does not affect primary breast tumor growth but strongly inhibits pulmonary metastasis. We conclude that mitochondrial 1C metabolism, despite being dispensable for proliferative capacities, confers an advantage to cancer cells by supporting their motility potential.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30363-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30363-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30363-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().