Anti-FOXF2 monoclonal antibody, clone 4G6

Forkhead box (FOX) F2 and FOXC2 belong to the FOX transcription factor superfamily. FOXC2 is recognized as an inducer of epithelial mesenchymal transition (EMT), and its overexpression promotes basal-like breast cancer (BLBC) metastasis. Our previous study demonstrated that FOXF2 functions as an EMT suppressor and that FOXF2 deficiency promotes BLBC metastasis. However, the relationship between the opposite EMT-related transcription factors FOXF2 and FOXC2 remains unknown. Here, we found that FOXF2 directly targets FOXC2 to negatively regulate FOXC2 transcription in BLBC cells. Functionally, we observed that FOXC2 mediates the FOXF2-regulated EMT phenotype, aggressive behavior, and multiple chemotherapy drug resistance of BLBC cells. Additionally, we detected a significant negative correlation between the FOXF2 and FOXC2 mRNA levels in triple-negative breast cancer (TNBC) tissues. TNBC patients in the FOXF2(high)/FOXC2(low) and FOXF2(low)/FOXC2(high) groups exhibited the best and worst disease-free survival (DFS), respectively, whereas the patients in the FOXF2(high)/FOXC2(high) and FOXF2(low)/FOXC2(low) groups exhibited moderate DFS. In summary, we found that FOXF2 transcriptionally targets FOXC2 and suppresses EMT and multidrug resistance by negatively regulating the transcription of FOXC2 in BLBC cells. The combined expression levels of FOXF2 and FOXC2 mRNA might serve as an effective prognostic indicator and could guide tailored therapy for TNBC or BLBC patients. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ac-nd/4.0/).

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer (BC), is characterized as high proliferation, young age and poor prognosis. MicroRNA-182 (miR-182) was reported to have oncogenic potential in many cancers. We aimed to elucidate pathobiological effects of miR-182 expression by targeting forkhead-box F2 (FOXF2) in TNBC. In this study, we explored the functional role of miR-182 expression in TNBC. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the expression of miR-182 in cell lines and tissues. A series of in vitro and in vivo assays were performed in the MCF-7 and MDA-MB-231 cell lines with miR-182 overexpression. Luciferase reporter assays and western blot analysis were used to identify FOXF2 as the direct and functional target of miR-182. In TNBC tissues and cell lines, we found that miR-182 was significantly upregulated. Transwell assay showed that re-expression of miR-182 increased cell migration and invasion abilities and MTT assay showed that it promoted cell growth in vitro. In vivo assay, re-expression of miR-182 significantly increase tumor volume and enhanced instant metastasis in the lungs of mice. Besides, FOXF2 was identified as a direct and functional target of miR-182. These results indicated that miR-182 plays an important role in the initiation and progression of TNBC by targeting FOXF2 and the miR-182/FOXF2 axis may present a new therapeutic strategy for TNBC in the future.