Krüppel-Like Factor 4 (KLF4) functions as a tumor suppressor in some cancers, 
but its molecular mechanism is not clear. Our recent study also showed that the 
expression of KLF4 is dramatically reduced in primary lung cancer tissues. To 
investigate the possible role of KLF4 in lung cancer, we stably transfected KLF4 
into cells from lung cancer cell lines H322 and A549 to determine the cells' 
invasion ability. Our results showed that ectopic expression of KLF4 extensively 
suppressed lung cancer cell invasion in Matrigel. This effect was independent of 
KLF4-mediated p21 up-regulation because ectopic expression of p21 had minimal 
effect on cell invasion. Our analysis of the expression of 12 genes associated 
with cell invasion in parental, vector-transfected, and KLF4-transfected cells 
showed that ectopic expression of KLF4 resulted in extensively repressed 
expression of secreted protein acidic and rich in cysteine (SPARC), an 
extracellular matrix protein that plays a role in tumor development and 
metastasis. Knockdown of SPARC expression in H322 and A549 cells led to 
suppression of cell invasion, comparable to that observed in KLF4-transfected 
cells. Moreover, retrovirus-mediated restoration of SPARC expression in 
KLF4-transfected cells abrogated KLF4-induced anti-invasion activity. Together, 
our results indicate that KLF4 inhibits lung cancer cell invasion by suppressing 
SPARC gene expression.