LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis

M. C. Poffenberger, A. Metcalfe-Roach, E. Aguilar, J. Chen, B. E. Hsu, A. H. Wong, R. M. Johnson, B. Flynn, B. Samborska, E. H. Ma, S. P. Gravel, L. Tonelli, L. Devorkin, P. Kim, A. Hall, S. Izreig, E. Loginicheva, N. Beauchemin, P. M. Siegel, M. N. ArtyomovJ. J. Lum, G. Zogopoulos, J. Blagih, R. G. Jones

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish
Pages (from-to)406-411
Number of pages6
Issue number6400
StatePublished - Jul 27 2018


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