FOXF2 oppositely regulates stemness in luminal and basal-like breast cancer cells through the Wnt/beta-catenin pathway.

The stemness of cancer cells contributes to tumorigenesis, the heterogeneity of malignancies, cancer metastasis, and therapeutic resistance. However, the roles and regulatory mechanisms maintaining stemness among breast cancer subtypes remain elusive. Our previous studies have demonstrated that ectopic expression and dynamic alteration of the mesenchymal transcription factor forkhead box F2 (FOXF2) differentially regulates breast cancer progression and metastasis organotropism in a cell subtype-specific manner. Here, we reveal the underlying mechanism by which FOXF2 enhances stemness in luminal breast cancer cells but suppresses that in basal-like breast cancer (BLBC) cells. We show that luminal breast cancer and BLBC cells with FOXF2-regulated stemness exhibit partial mesenchymal stem cell properties that toward osteogenic differentiation and myogenic differentiation, respectively. Furthermore, we show that FOXF2 activates the Wnt signaling pathway in luminal breast cancer cells but represses this pathway in BLBC cells by recruiting nuclear receptor coactivator 3 (NCoA3) and nuclear receptor corepressor 1 (NCoR1) to the promoters of Wnt family member 2B (WNT2B) and frizzled class receptor 1 (FZD1) genes to activate and repress their transcription, respectively. We propose that targeting the Wnt signaling pathway is a promising strategy for the treatment of breast cancers with dysregulated expression of FOXF2.

Prognostic and Predictive Value of a 15 Transcription Factors (TFs) Panel for Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most devastating diseases worldwide. Limited performance of clinicopathologic parameters as prognostic factors underscores more accurate and effective biomarkers for high-confidence prognosis that guide decision-making for optimal treatment of HCC. The aim of the present study was to establish a novel panel to improve prognosis prediction of HCC patients, with a particular interest in transcription factors (TFs). MATERIALS AND METHODS: A TF-related prognosis model of liver cancer with data from ICGC-LIRP-JI cohort successively were processed by univariate and multivariate Cox regression analysis. Then, for evaluating the prognostic prediction value of the model, receiver operating characteristic (ROC) curve and survival analysis were performed both with internal data from the International Cancer Genome Consortium (ICGC) and external data from The Cancer Genome Atlas (TCGA). Furthermore, we verified the expression of three genes in HCC cell lines by Western blot and qPCR and protein expression level by IHC in liver cancer patients' sample. Finally, we constructed a TF clinical characteristics nomogram to furtherly predict liver cancer patient survival probability with TCGA cohort. RESULTS: By Cox regression analysis, a panel of 15 TFs (ZNF331, MYCN, AHRR, LEF1, ZNF780A, POU1F1, DLX5, ZNF775, PLSCR1, FOXK1, TAL2, ZNF558, SOX9, TCFL5, GSC) was identified to present with powerful predictive performance for overall survival of HCC patients based on internal ICGC cohort and external TCGA cohort. A nomogram that integrates these factors was established, allowing efficient prediction of survival probabilities and displaying higher clinical utility. CONCLUSION: The 15-TF panel is an independent prognostic factor for HCC, and 15 TF-based nomogram might provide implication an effective approach for HCC patient management and treatment.