The LKB1 tumor suppressor negatively regulates mTOR signaling Academic Article uri icon

Overview

MeSH Major

  • Gastrointestinal Tract
  • Hamartoma
  • Multienzyme Complexes
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Repressor Proteins
  • Signal Transduction

abstract

  • 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.

publication date

  • July 2004

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2004.06.007

PubMed ID

  • 15261145

Additional Document Info

start page

  • 91

end page

  • 9

volume

  • 6

number

  • 1