1. LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis
- Author
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Anita Hall, Russell G. Jones, A. Metcalfe-Roach, Lindsay DeVorkin, Luciana Tonelli, Bozena Samborska, Radia M. Johnson, Said Izreig, Breanna R. Flynn, Maya C. Poffenberger, Eric H. Ma, Alison H-T Wong, George Zogopoulos, Ekaterina Loginicheva, P. Kim, Simon-Pierre Gravel, Brian E. Hsu, Maxim N. Artyomov, N. Beauchemin, Julian J. Lum, Jocelyn Chen, Esther Aguilar, Julianna Blagih, and Peter M. Siegel
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,T-Lymphocytes ,Chemokine CXCL2 ,Peutz-Jeghers Syndrome ,STK11 ,Gene Expression ,Inflammation ,AMP-Activated Protein Kinases ,Protein Serine-Threonine Kinases ,Adenomatous Polyps ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Stomach Neoplasms ,medicine ,Animals ,Humans ,Interleukin 6 ,STAT3 ,Multidisciplinary ,biology ,Interleukin-6 ,Kinase ,business.industry ,Interleukin-11 ,Mice, Mutant Strains ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,STAT protein ,medicine.symptom ,Signal transduction ,business ,Gene Deletion ,Signal Transduction - Abstract
Inflammation promotes gut polyposis Peutz–Jeghers Syndrome (PJS) causes benign polyps in the gut and a higher risk of several cancers caused by mutations in the tumor suppressor gene STK11 , which encodes liver kinase B1 (LKB1). LKB1's role in this disease is thought to be related to its tumor suppressor function. Now, Poffenberger et al. show that the T cell–specific heterozygous deletion of Stk11 is sufficient to reproduce PJS symptoms in mice (see the Perspective by Hollstein and Shaw). Polyps in mice and humans are characterized by immune cell infiltration, enhanced STAT3 signaling, and increased levels of inflammatory cytokines such as interleukin-6 (IL-6). Targeting STAT3 signaling, IL-6, or T cells ameliorated the polyps, suggesting potential therapies for this disease. Science , this issue p. 406 ; see also p. 332
- Published
- 2018
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