Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2.

Pancreatic cancer (PC) is a malignant tumor possessing high mortality. The role of transcription factor Forkhead Box F2 (FOXF2) in PC remains unverified. The current study investigated the roles of FOXF2 in developing PC in vitro and in vivo. A xenograft tumor model was constructed with nude mice injected using FOXF2­overexpressing PC cells or FOXF2­silenced PC cells. High FOXF2 expression significantly enhanced the proliferation ability of PC cells in vitro and pancreatic tumor growth in vivo. The cell cycle analysis indicated that transition of G1­S phase was promoted by FOXF2. The cell cycle­associated proteins cyclin D1, CDK2, phosphorylated (p)­CDK2 and p­RB were upregulated in the FOXF2­overexpressing cells and downregulated in the cells with FOXF2 knockdown. Flow cytometric analysis and Hoechst staining showed that the percentage of apoptotic cells was significantly increased after FOXF2 was silenced. FOXF2 knockdown promoted expression of pro­apoptotic proteins (Bad, Bax and cleaved caspase­3) while suppressing the anti­apoptotic proteins (Bcl­2 and Bcl­xl) at the protein level. FOXF2 improved the migration and invasion of PC cells in vitro. Moreover, luciferase and chromatin immunoprecipitation assays revealed that FOXF2 binds to the MSI2 promoter, promoting its transcriptional expression. FOXF2 knockdown inhibited the MSI2 protein translation while enhancing the translation of NUMB protein, suppressing PC development in vivo. MSI2 silencing reversed the promotive effect mediated by FOXF2 on cell proliferation. These results demonstrated that FOXF2 is essential in PC progression, and the potential mechanism includes regulating MSI2 transcription.

The implication of ciliary signaling pathways for epithelial-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT), which plays an essential role in development, tissue repair and fibrosis, and cancer progression, is a reversible cellular program that converts epithelial cells to mesenchymal cell states characterized by motility-invasive properties. The mostly signaling pathways that initiated and controlled the EMT program are regulated by a solitary, non-motile organelle named primary cilium. Acting as a signaling nexus, primary cilium dynamically concentrates signaling molecules to respond to extracellular cues. Recent research has provided direct evidence of connection between EMT and primary ciliogenesis in multiple contexts, but the mechanistic understanding of this relationship is complicated and still undergoing. In this review, we describe the current knowledge about the ciliary signaling pathways involved in EMT and list the direct evidence that shows the link between them, trying to figure out the intricate relationship between EMT and primary ciliogenesis, which may aid the future development of primary cilium as a novel therapeutic approach targeted to EMT.