Upregulation of DLX5 Promotes Ovarian Cancer Cell Proliferation by Enhancing IRS-2-AKT Signaling

摘要: The distal-less homeobox gene (dlx) 5 encodes a transcription factor that controls jaw formation and appendage differentiation during embryonic development. We had previously found Dlx5 is overexpressed in an Akt2 transgenic model of T-cell lymphoma. To investigate if DLX5 involved human cancer, we screened its expression the NCI 60 cancer cell line panel. was frequently upregulated lines derived from several tumor types, including ovarian cancer. next validated upregulation primary specimens. Stable knockdown by lentivirus-mediated transduction short hairpin RNA (shRNA) resulted reduced proliferation cells due to inhibition cycle progression connection with downregulation cyclins A, B1, D1, D2, E, decreased phosphorylation AKT. Cell resumed following introduction cDNA harboring wobbled mutations at shRNA-targeting sites. also rescued constitutively active form Intriguingly, IRS-2 MET contributed suppression AKT signaling. Moreover, directly bind promoter augmented transcription. Knockdown xenografts markedly diminished size. In addition, cooperate HRAS transformation surface epithelial cells. Together, these data suggest plays significant role pathogenesis some cancers.