Loss of attachment promotes proline accumulation and excretion in cancer cells

Steven E. Pilley, Marc Hennequart, Anke Vandekeere, Julianna Blagih, Nathalie M. Legrave, Sarah Maria Fendt, Karen H. Vousden*, Christiaan F. Labuschagne

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline incorporation into proteins was lower in detached cells compared to other amino acids, there was an increased production of the proline-rich protein collagen. The increased excretion of proline from detached cells was also shown to be used by macrophages, an abundant and important component of the tumor microenvironment. Our study suggests that detachment induced accumulation and secretion of proline may contribute to tumor progression by supporting increased production of extracellular matrix and providing proline to surrounding stromal cells.

Original languageEnglish
Article numbereadh2023
JournalScience advances
Volume9
Issue number36
DOIs
Publication statusPublished - 8 Sept 2023
Externally publishedYes

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