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Tumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availabilityстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 8 апреля 2021 г.
- Авторы: Won Dong Lee, Pirona Anna Chiara, Sarvin Boris, Stern Alon, Nevo-Dinur Keren, Besser Elazar, Sarvin Nikita, Lagziel Shoval, Mukha Dzmitry, Raz Shachar, Aizenshtein Elina, Shlomi Tomer
- Журнал: Cell Metabolism
- Том: 1
- Номер: 33
- Год издания: 2021
- Издательство: Cell Press
- Местоположение издательства: United States
- Первая страница: 190
- Последняя страница: 198.e6
- DOI: 10.1016/j.cmet.2020.12.002
- Аннотация: Folate metabolism supplies one-carbon (1C) units for biosynthesis and methylation and has long been a target for cancer chemotherapy. Mitochondrial serine catabolism is considered the sole contributor of folate-mediated 1C units in proliferating cancer cells. Here, we show that under physiological folate levels in the cell environment, cytosolic serine-hydroxymethyltransferase (SHMT1) is the predominant source of 1C units in a variety of cancers, while mitochondrial 1C flux is overly repressed. Tumor-specific reliance on cytosolic 1C flux is associated with poor capacity to retain intracellular folates, which is determined by the expression of SLC19A1, which encodes the reduced folate carrier (RFC). We show that silencing SHMT1 in cells with low RFC expression impairs pyrimidine biosynthesis and tumor growth in vivo. Overall, our findings reveal major diversity in cancer cell utilization of the cytosolic versus mitochondrial folate cycle across tumors and SLC19A1 expression as a marker for increased reliance on SHMT1. These authors contributed equally: Won Dong Lee, Anna Chiara Pirona, Boris Sarvin
- Добавил в систему: Сарвин Борис Андреевич