LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis

doi:10.1126/science.aan3975

GSTDTAP > 地球科学

DOI	10.1126/science.aan3975
	LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis
	Poffenberger, M. C.1,2; Metcalfe-Roach, A.1; Aguilar, E.1,2; Chen, J.1,2; Hsu, B. E.1,3; Wong, A. H.1,2; Johnson, R. M.1,4; Flynn, B.1,2; Samborska, B.1; Ma, E. H.1,2; Gravel, S-P 1,5; Tonelli, L.1; Devorkin, L.6; Kim, P.6; Hall, A.1,7; Izreig, S.1,2; Loginicheva, E.8; Beauchemin, N.1,9; Siegel, P. M.1,3; Artyomov, M. N.8,10; Lum, J. J.6,11; Zogopoulos, G.1,7; Blagih, J.1,2; Jones, R. G.1,2,12
	2018-07-27
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2018
卷号	361 期号:6400 页码:406-411
文章类型	Article
语种	英语
国家	Canada; USA
英文摘要	Germline mutations in STK11, which encodes the tumor suppressor liver kinase B1 (LKB1). promote Peutz-Jeghers syndrome (PJS), a cancer predisposition syndrome characterized by the development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion of Stk11 in T cells (LThet mice) is sufficient to promote GI polyposis. Polyps from LThet mice, Stk11(+/-) mice, and human PJS patients display hallmarks of chronic inflammation, marked by inflammatory immune-cell infiltration, signal transducer and activator of transcription 3 (STAT3) activation, and increased expression of inflammatory factors associated with cancer progression [interleukin 6 (IL-6), IL-11 and CXCL2]. Targeting either T cells, IL-6, or STAT3 signaling reduced polyp growth in Stk11(+/-) animals. Our results identify LKB1-mediated inflammation as a tissue-extrinsic regulator of intestinal polyposis in PJS, suggesting possible therapeutic approaches by targeting deregulated inflammation in this disease.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000439923700044
WOS关键词	PEUTZ-JEGHERS-SYNDROME ; HEMATOPOIETIC STEM-CELLS ; GASTRIC TUMORIGENESIS ; INTESTINAL POLYPOSIS ; KNOCKOUT MICE ; METABOLISM ; CANCER ; INFLAMMATION ; STAT3 ; IL-6
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/199253
专题	地球科学资源环境科学气候变化
作者单位	1.McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada; 2.McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada; 3.McGill Univ, Dept Med, Montreal, PQ H3G 2M1, Canada; 4.Genentech Inc, 1 DNA Way South, San Francisco, CA 94080 USA; 5.Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada; 6.BC Canc Agcy, Trev & Joyce Deeley Res Ctr, Victoria, BC V8R 6V5, Canada; 7.McGill Univ, Hlth Ctr, Res Inst, Montreal, PQ H3H 2R9, Canada; 8.Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA; 9.McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada; 10.Washington Univ, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA; 11.Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 2Y2, Canada; 12.Van Andel Res Inst, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA
推荐引用方式 GB/T 7714	Poffenberger, M. C.,Metcalfe-Roach, A.,Aguilar, E.,et al. LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis[J]. SCIENCE,2018,361(6400):406-411.
APA	Poffenberger, M. C..,Metcalfe-Roach, A..,Aguilar, E..,Chen, J..,Hsu, B. E..,...&Jones, R. G..(2018).LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis.SCIENCE,361(6400),406-411.
MLA	Poffenberger, M. C.,et al."LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis".SCIENCE 361.6400(2018):406-411.