Stat3 regulates genes common to both wound healing and cancer.
Wound healing and cancer are both characterized by cell proliferation, remodeling of extracellular matrix, cell invasion and migration, new blood vessel formation, and modulation of blood coagulation. The mechanisms that link wound healing and cancer are poorly understood. We report here that Stat3, a common signaling mechanism involved in oncogenesis and tissue injury, regulates a common set of genes involved in wound healing and cancer. Using oligonucleotide gene arrays and quantitative real-time PCR, we evaluated changes in global gene expression resulting from expression of Stat3 in lung epithelial cells. We report here previously uncharacterized genes induced by Stat3 implicated in signaling pathways common to both wound healing and cancer including cell invasion and migration, angiogenesis, modulation of coagulation, and repression of interferon-inducible genes. Consistent with these results, we found increased Stat3 activity associated with wound healing in chronically inflamed mouse lungs and increased Stat3 activity was identified at the leading edge of lung tumors invading adjacent nontumor stroma. These findings provide a molecular basis for understanding cancer as a deregulation of normal wound healing processes.
Dauer
Daniel J
DJ
Thoracic Oncology/Experimental Therapeutics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Ferraro
Bernadette
B
Song
Lanxi
L
Yu
Bin
B
Mora
Linda
L
Buettner
Ralf
R
Enkemann
Steve
S
Jove
Richard
R
Haura
Eric B
EB
D000209:Acute-Phase Proteins; D000818:Animals; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells; D020869:Gene Expression Profiling; D007249:Inflammation; D008168:Lung / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000494:pharmacology*; D014945:Wound Healing / Q000235:genetics*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators