Critical regulation of genes for tumor cell migration by AP-1

Clin Exp Metastasis. 2004;21(4):293-304. doi: 10.1023/b:clin.0000046132.46946.dd.


The AP-1 transcription factor plays a critical role in regulating tumor cell proliferation and has been implicated in controlling a program of gene expression that mediates cell motility and invasion in vitro. We have utilized two dominant negative AP-1 constructs, TAM67 and aFos, each fused to GFP, to investigate the role of AP-1 complexes in an invasive, clinically derived human tumor cell line, HT-1080. As expected, high levels of both GFP-TAM67 and GFP-aFos arrested HT-1080 cells in the G1 phase of the cell cycle. Strikingly, at low levels GFP-aFos, but not GFP-TAM67, caused a change in colony morphology, impairment of directional motility in a monolayer wound healing assay, as well as inhibition of chemotaxis and haptotaxis. Microarray analysis identified a novel set of AP-1 target genes, including the tumor suppressor TSCL-1 and regulators of actin cytoskeletal dynamics, including the gelsolin-like actin capping protein CapG. The demonstration that AP-1 regulates the expression of genes involved in tumor cell motility and cytoskeletal dynamics in a clinically derived human tumor cell line identifies new pathways of control for tumor cell motility.

Publication types

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

MeSH terms

  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cell Line, Tumor
  • Cell Movement*
  • Chemotaxis
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology*
  • G1 Phase
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoglobulins / genetics
  • Membrane Proteins / genetics
  • Microfilament Proteins / genetics
  • Nuclear Proteins / genetics
  • Peptide Fragments / physiology
  • Proto-Oncogene Proteins c-jun / physiology
  • Transcription Factor AP-1 / physiology*
  • Tumor Suppressor Proteins


  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Membrane Proteins
  • Microfilament Proteins
  • Nuclear Proteins
  • Peptide Fragments
  • Proto-Oncogene Proteins c-jun
  • TAM67 peptide
  • Transcription Factor AP-1
  • Tumor Suppressor Proteins
  • CAPG protein, human