Author
Listed:
- Ilaria Elia
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Matteo Rossi
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Steve Stegen
(Metabolism and Ageing, KU Leuven)
- Dorien Broekaert
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Ginevra Doglioni
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Marit van Gorsel
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Ruben Boon
(Stem Cell Institute, KU Leuven)
- Carmen Escalona-Noguero
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
- Sophie Torrekens
(Metabolism and Ageing, KU Leuven)
- Catherine Verfaillie
(Stem Cell Institute, KU Leuven)
- Erik Verbeken
(KU Leuven)
- Geert Carmeliet
(Metabolism and Ageing, KU Leuven)
- Sarah-Maria Fendt
(VIB-KU Leuven Center for Cancer Biology, VIB
Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI))
Abstract
The extracellular matrix is a major component of the local environment—that is, the niche—that determines cell behaviour1. During metastatic growth, cancer cells shape the extracellular matrix of the metastatic niche by hydroxylating collagen to promote their own metastatic growth2,3. However, only particular nutrients might support the ability of cancer cells to hydroxylate collagen, because nutrients dictate which enzymatic reactions are active in cancer cells4,5. Here we show that breast cancer cells rely on the nutrient pyruvate to drive collagen-based remodelling of the extracellular matrix in the lung metastatic niche. Specifically, we discovered that pyruvate uptake induces the production of α-ketoglutarate. This metabolite in turn activates collagen hydroxylation by increasing the activity of the enzyme collagen prolyl-4-hydroxylase (P4HA). Inhibition of pyruvate metabolism was sufficient to impair collagen hydroxylation and consequently the growth of breast-cancer-derived lung metastases in different mouse models. In summary, we provide a mechanistic understanding of the link between collagen remodelling and the nutrient environment in the metastatic niche.
Suggested Citation
Ilaria Elia & Matteo Rossi & Steve Stegen & Dorien Broekaert & Ginevra Doglioni & Marit van Gorsel & Ruben Boon & Carmen Escalona-Noguero & Sophie Torrekens & Catherine Verfaillie & Erik Verbeken & Ge, 2019.
"Breast cancer cells rely on environmental pyruvate to shape the metastatic niche,"
Nature, Nature, vol. 568(7750), pages 117-121, April.
Handle:
RePEc:nat:nature:v:568:y:2019:i:7750:d:10.1038_s41586-019-0977-x
DOI: 10.1038/s41586-019-0977-x
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Cited by:
- Miao Yan & Qing Chen & Tianyi Liu & Xiaofeng Li & Peng Pei & Lei Zhou & Shan Zhou & Runhao Zhang & Kang Liang & Jian Dong & Xunbin Wei & Jinqiang Wang & Osamu Terasaki & Pu Chen & Zhen Gu & Libo Jiang, 2023.
"Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma,"
Nature Communications, Nature, vol. 14(1), pages 1-15, December.
- C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023.
"Metabolic dependencies of metastasis-initiating cells in female breast cancer,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
- Zhiyuan Yuan & Yisi Li & Minglei Shi & Fan Yang & Juntao Gao & Jianhua Yao & Michael Q. Zhang, 2022.
"SOTIP is a versatile method for microenvironment modeling with spatial omics data,"
Nature Communications, Nature, vol. 13(1), pages 1-19, December.
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