Aberrant regulation of serine metabolism drives extracellular vesicle release and cancer progression.

Autor:	Yamamoto T; Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan; Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan; Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kanagawa, Japan., Nakayama J; Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan; Department of Oncogenesis and Growth Regulation, Research Institute, Osaka International Cancer Institute, Osaka, Japan., Urabe F; Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan., Ito K; Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan., Nishida-Aoki N; Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan., Kitagawa M; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, Nagoya, Japan., Yokoi A; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Nagoya University Institute for Advanced Research, Nagoya, Japan., Kuroda M; Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan., Hattori Y; Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan., Yamamoto Y; Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan. Electronic address: yuyamamo@ncc.go.jp., Ochiya T; Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan. Electronic address: tochiya@tokyo-med.ac.jp.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114517. Date of Electronic Publication: 2024 Jul 17.
DOI:	10.1016/j.celrep.2024.114517
Abstrakt:	Cancer cells secrete extracellular vesicles (EVs) to regulate cells in the tumor microenvironment to benefit their own growth and survive in the patient's body. Although emerging evidence has demonstrated the molecular mechanisms of EV release, regulating cancer-specific EV secretion remains challenging. In this study, we applied a microRNA library to reveal the universal mechanisms of EV secretion from cancer cells. Here, we identified miR-891b and its direct target gene, phosphoserine aminotransferase 1 (PSAT1), which promotes EV secretion through the serine-ceramide synthesis pathway. Inhibition of PSAT1 affected EV secretion in multiple types of cancer, suggesting that the miR-891b/PSAT1 axis shares a common mechanism of EV secretion from cancer cells. Interestingly, aberrant PSAT1 expression also regulated cancer metastasis via EV secretion. Our data link the PSAT1-controlled EV secretion mechanism and cancer metastasis and show the potential of this mechanism as a therapeutic target in multiple types of cancer. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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