气候变化领域集成服务门户(CCPortal): Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells

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DOI	10.1073/pnas.2101268118
	Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells
	Wang J.; Filippakis H.; Hougard T.; Du H.; Ye C.; Liu H.-J.; Zhang L.; Hindi K.; Bagwe S.; Nijmeh J.; Asara J.M.; Shi W.; El-Chemaly S.; Henske E.P.; Lam H.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:39
英文摘要	Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either TSC1 or TSC2. Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking up-regulation of Interleukin-6 (IL-6). LAM patient plasma contained increased circulating IL-6 compared with healthy controls, and TSC2-deficient cells showed up-regulation of IL-6 transcription and secretion compared to wild-type cells. IL-6 blockade repressed the proliferation and migration of TSC2-deficient cells and reduced oxygen consumption and extracellular acidification. U-13C glucose tracing revealed that IL-6 knockout reduced 3-phosphoserine and serine production in TSC2-deficient cells, implicating IL-6 in de novo serine metabolism. IL-6 knockout reduced expression of phosphoserine aminotransferase 1 (PSAT1), an essential enzyme in serine biosynthesis. Importantly, recombinant IL- 6 treatment rescued PSAT1 expression in the TSC2-deficient, IL-6 knockout clones selectively and had no effect on wild-type cells. Treatment with anti-IL-6 (αIL-6) antibody similarly reduced cell proliferation and migration and reduced renal tumors in Tsc2+/- mice while reducing PSAT1 expression. These data reveal a mechanism through which IL-6 regulates serine biosynthesis, with potential relevance to the therapy of tumors with mTORC1 hyperactivity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Interleukin 6; Lymphangioleiomyomatosis; MTORC1; Phosphoserine aminotransferase 1 (PSAT1); Tuberous sclerosis complex
语种	英语
scopus关键词	aminotransferase; interleukin 6; mammalian target of rapamycin complex 1; phosphoserine aminotransferase; serine; TSC2 protein, human; Tsc2 protein, mouse; tuberin; animal; C57BL mouse; genetics; knockout mouse; metabolism; mouse; physiology; Animals; Interleukin-6; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Inbred C57BL; Mice, Knockout; Serine; Transaminases; Tuberous Sclerosis Complex 2 Protein
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238371
作者单位	Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, United States; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, United States; Department of Surgery, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, United States
推荐引用方式 GB/T 7714	Wang J.,Filippakis H.,Hougard T.,et al. Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells[J],2021,118(39).
APA	Wang J..,Filippakis H..,Hougard T..,Du H..,Ye C..,...&Lam H.C..(2021).Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America,118(39).
MLA	Wang J.,et al."Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells".Proceedings of the National Academy of Sciences of the United States of America 118.39(2021).