Lymphangioleiomyomatosis - a wolf in sheep's clothing

J Clin Invest. 2012 Nov;122(11):3807-16. doi: 10.1172/JCI58709. Epub 2012 Nov 1.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Proliferation
  • Female
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Lymphangioleiomyomatosis* / genetics
  • Lymphangioleiomyomatosis* / metabolism
  • Lymphangioleiomyomatosis* / pathology
  • Mutation
  • Myocytes, Smooth Muscle* / metabolism
  • Neoplasm Metastasis
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Tumor Suppressor Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases