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Abstract Inactive somatic mutations resulting in loss of function of the tumor suppressor gene STK11 (serine-threonine kinase 11), which encodes LKB1 protein (liver kinase B1), frequently occur in several sporadic cases. cancers, including lung, pancreatic and reproductive tumors. In addition, inherited heterozygous genetic mutations in STK11 cause Peutz-Jeghers Syndrome (PJS), a syndrome predisposed to cancer ( 1 ). One characteristic of PJS is the growth of many benign gastrointestinal hamartomatous polyps (GIs) and a high risk of developing malignant tumors in several organs ( 2 ). Studies in mouse models of PJS have shown that deficiency of LKB1 in the stroma, and not the epithelium, was the contributing factor to the formation of gastrointestinal polyps ( 3 ). Stroma includes fibroblasts, smooth muscle, extracellular matrix, and basement membrane that support epithelial tissue. However, how deficiency in LKB1 in stromal cells could trigger polyp formation was not clear. Two recent studies now shed light on the mechanism of PJS polyp formation. On page 406 of this issue, Poffenberger and others ( 4 ) find that the loss of a single Stk11 allele in T cells is sufficient to cause the formation of gastrointestinal polyps. Similarly, a study by Ollila and others ( ) demonstrated that the heterozygous loss of Stk11 in gastric stromal cells was sufficient to cause the formation of gastrointestinal polyps. Transcriptional profiling in both studies revealed a positive regulation of inflammatory cytokines involved in promoting the expansion and proliferation of stroma and normal GI epithelium. Finding that inflammation in the stromal compartment due to loss of LKB1 in T cells ( 4 ) or stromal cells ( 5 ) results in the formation of polyps, these studies highlight how inflammatory signals can profoundly alter the microenvironment and the formation of combustible tumors.
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