Additional file 1: Figure S3. of Forkhead Box F1 promotes breast cancer cell migration by upregulating lysyl oxidase and suppressing Smad2/3 signaling

FoxF1-induced upregulation of LOX increases invasiveness. An additional siRNA against LOX was used to confirm the effect of LOX depletion on invasive capacity of HC11FoxF1 cells shown in Fig. 3b. A, densitometry of western blot analysis of supernatant with LOX antibody after transfection with LOX siRNA or mock-treatment. B, relative invasion capacity following LOX RNAi. (PDF 286 kb

Additional file 3: Figure S1. of Forkhead Box F1 promotes breast cancer cell migration by upregulating lysyl oxidase and suppressing Smad2/3 signaling

NFI-C2 and FoxF1 regulates expression of genes involved in EMT. Reverse transcription PCR analysis of Desmoglein 1β, Twist1, Zeb1, Snail1 and GAPDH mRNA levesl in parental, NFI-C2- or FoxF1-overexpressing HC11 cells. (PDF 475 kb

Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1.

Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis. Cancer Res; 70(5); OF1-10