TFAP2C (
transcription factor-activating enhancer-
binding protein 2C) expression has been positively correlated with poor
prognosis in
patients with certain types of
cancer, but the mechanisms underlying TFAP2C-mediated
tumorigenesis in non-small-
cell lung cancer (NSCLC) are still unknown. We previously performed a
microarray analysis to identify TFAP2C
regulation genes, and
TGFBR1 (
transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or
TGFBR1 overexpression led to oncogenic properties, such as
cell viability, proliferation and
cell cycle progression.
TGFBR1 upregulation induced by TFAP2C also promoted
cell motility and migration, leading to malignant development. We also found that PAK1 (p21
protein (Cdc42/Rac)-activated
kinase 1) signaling was involved in TFAP2C/
TGFBR1-induced
tumorigenesis. These results were confirmed by an in vivo
xenograft model and
patient tissue samples. This study shows that TFAP2C promoted
tumor progression by
upregulation of
TGFBR1 and consequent activation of PAK1 signaling.