Germline mutations in LKB1, TSC2, or PTEN tumor suppressor genes result in 
hamartomatous syndromes with shared tumor biological features. The recent 
observations of LKB1-mediated activation of AMP-activated protein kinase (AMPK) 
and AMPK inhibition of mTOR through TSC2 prompted us to examine the biochemical 
and biological relationship between LKB1 and mTOR regulation. Here, we report 
that LKB1 is required for repression of mTOR under low ATP conditions in 
cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs 
and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show 
elevated signaling downstream of mTOR. These findings position aberrant mTOR 
activation at the nexus of these germline neoplastic conditions and suggest the 
use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome.