NKX2-1/TTF-1: an enigmatic oncogene that functions as a double-edged sword for cancer cell survival and progression

Cancer Cell. 2013 Jun 10;23(6):718-23. doi: 10.1016/j.ccr.2013.04.002.


Emerging evidence indicates that NKX2-1, a homeobox-containing transcription factor also known as TTF-1, plays a role as a "lineage-survival" oncogene in lung adenocarcinomas. In T cell acute lymphoblastic leukemia, gene rearrangements lead to aberrant expression of NKX2-1/TTF-1. Despite accumulating evidence supporting its oncogenic role, it has become apparent that NKX2-1/TTF-1 expression also has biological and clinical functions in the opposite direction that act against tumor progression. Herein, we review recent findings showing these enigmatic double-edged characteristics, with special attention given to the roles of NKX2-1/TTF-1 in lung development and carcinogenesis.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Animals
  • Cell Survival / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Humans
  • Lung / embryology
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • Homeodomain Proteins
  • NKX2-1 protein, human
  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors