The LKB1 Tumor Suppressor Kinase in Human Disease

Biochim Biophys Acta. 2007 Jan;1775(1):63-75. doi: 10.1016/j.bbcan.2006.08.003. Epub 2006 Aug 16.

Abstract

Inactivating germline mutations in the LKB1 gene underlie Peutz-Jeghers syndrome characterized by hamartomatous polyps and an elevated risk for cancer. Recent studies suggest the involvement of LKB1 also in more common human disorders including diabetes and in a significant fraction of lung adenocarcinomas. These observations have increased the interest towards signaling pathways of this tumor suppressor kinase. The recent breakthroughs in understanding the molecular functions of the LKB1 indicate its contribution as a regulator of cell polarity, energy metabolism and cell proliferation. Here we review how the substrates and cellular functions of LKB1 may be linked to Peutz-Jeghers syndrome and other diseases, and discuss how some of the molecular changes associated with altered LKB1 signaling might be used in therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / genetics
  • Animals
  • Cell Polarity / physiology
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Humans
  • Lung Neoplasms / genetics
  • Mice
  • Peutz-Jeghers Syndrome / genetics
  • Peutz-Jeghers Syndrome / physiopathology
  • Peutz-Jeghers Syndrome / therapy
  • Protein Kinases / physiology
  • Protein-Serine-Threonine Kinases / physiology*
  • Signal Transduction
  • Tumor Suppressor Proteins / physiology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Tumor Suppressor Proteins
  • Protein Kinases
  • AMP-activated protein kinase kinase
  • STK11 protein, human
  • Protein-Serine-Threonine Kinases