Up-regulation of Foxp3 inhibits cell proliferation, migration and invasion in epithelial ovarian cancer.
The transcription factor Forkhead Box P3 (Foxp3) has been shown to play important roles in the occurring of regulatory T cells (Tregs). Limited evidence indicated that it was also expressed in tissues other than thymus and spleen, while, very recently, it was identified as a suppressor gene in breast cancer. However, the precise role and molecular mechanism of the action of Foxp3 in ovarian cancer remained unclear. To elucidate the function of Foxp3, we examined the expression of Foxp3 in ovarian cancerous cells and the consequences of up-regulation of Foxp3 in epithelial ovarian cancer cell lines, respectively. By multiple cellular and molecular approaches such as gene transfection, CCK-8 assay, flow cytometry, RT-PCR, in-cell western, wound healing assay, and invasion assay, we found that Foxp3 was weakly/no expressed in ovarian cancerous cells. Up-regulation of Foxp3 inhibited cell proliferation, decreased cell migration, and reduced cell invasion. Compared with control, Foxp3 up-regulated cells showed decreased expression of Ki-67 and cyclin-dependent kinases (CDKs). Moreover, up-regulation of Foxp3 reduced the expression of matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (uPA), resulting in the inhibition of cell migration and invasion. In addition, Foxp3 up-regulation inhibited the activation of mammalian target of rapamycin (mTOR) and NF-kappaB signaling. These findings suggested that up-regulation of Foxp3 could be a novel approach for inhibiting ovarian cancer progression.
Zhang
Hai-Yan
HY
The Hospital of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, PR China.
Sun
Hong
H
D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases