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Background: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). Methods: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. Results: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrencefree survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial–mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Coimmunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. Conclusions: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Alveolar rhabdomyosarcomas of the mediastinum in children are rarely reported. Multimodality therapy including chemotherapy, surgery and radiotherapy make up the backbone of the treatment of childhood rhabdomyosarcomas. Complete resection whenever achievable is an important prognostic factor. However, complete resection of tumors in the mediastinum often poses a unique challenge to thoracic surgeons due to their close proximity to important neurovascular structures. Complete resection may not always be possible and judicious peri-operative planning and preparation are required to avoid creating unnecessary surgical morbidities resulting in delay of adjuvant therapy. Case presentation: A 4-month-old Chinese baby boy was presented to our hospital with stridor, shortness of breath and episodes of cyanosis. Imaging studies found an anterior mediastinal mass compressing the trachea and other neurovascular structures and he was diagnosed to have alveolar rhabdomyosarcoma. Our patient received upfront chemotherapy and subsequently open resection of the mass was attempted via median sternotomy. Intraoperatively, the mass had invaded into the great vessels, precluding a complete resection. Debulking surgery was performed instead and our patient received timely postoperative chemoradiotherapy. Conclusions: We report a rare case of childhood alveolar rhabdomyosarcoma of the mediastinum with vascular invasion treated with chemoradiotherapy and debulking surgery. Complete resection was not possible due to the close proximity to the great vessels. Different surgical approaches to the mediastinum have been reported in adults and children alike. Regardless of the surgical access, the treatment of childhood rhabdomyosarcomas should be individualized, with careful balance between surgical clearance and surgical morbidity. [ABSTRACT FROM AUTHOR]