Critical regulation of genes for tumor cell migration by AP-1.
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.
Bahassi
El Mustapha
el M
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Karyala
Saikumar
S
Tomlinson
Craig R
CR
Sartor
Maureen A
MA
Medvedovic
Mario
M
Hennigan
Robert F
RF
D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis; D005354:Fibrosarcoma / Q000235:genetics / Q000473:pathology*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; C439528:TAM67 peptide; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; C066575:CAPG protein, human