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

Abstract

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.

• Authors: El Mustapha Bahassi, Saikumar Karyala, Craig R Tomlinson, Maureen A Sartor, Mario Medvedovic, Robert F Hennigan
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 21 Issue 4 Pg. 293-304 ( 2004) ISSN: 0262-0898 [Print] Netherlands
• PMID: 15554385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• Cell Adhesion Molecule-1
• Cell Adhesion Molecules
• Cell Line, Tumor
• Cell Movement
• Chemotaxis
• Fibrosarcoma (genetics, 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