BackgroundThe 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).MethodsOne 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.ResultsNSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free 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. Co-immunoprecipitation 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.ConclusionsFOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0700-1) contains supplementary material, which is available to authorized users.

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The use of cardiopulmonary bypass alone without global myocardial ischemia secondary to aortic crossclamping and cardioplegic cardiac arrest can trigger intense inflammatory responses.

Surgery of the descending and thoracoabdominal aorta has been associated with post-operative paraparesis or paraplegia. Different strategies, which can be operative or non-operative, have been developed to minimise the incidence of neurological complications after aortic surgery. This review serves to summarise the current practice of spinal cord protection during surgery of the descending thoracoabdominal aortic surgery. The pathophysiology of spinal cord ischaemia will also be explained. The incidence of spinal cord ischaemia and subsequent neurological complications was associated with (1) the duration and severity of ischaemia, (2) failure to establish spinal cord supply and (3) reperfusion injury. The blood supply of the spinal cord has been extensively studied and the significance of the artery of Adamkiewicz (ASA) being recognised. This helps us to understand the pathophysiology of spinal cord ischaemia during descending and thoracoabdominal aortic operation. Techniques of monitoring of spinal cord function using evoked potential have been developed. Preoperative identification of ASA facilitates the identification of critical intercostal vessels for reimplantation, resulting in re-establishment of spinal cord blood flow. Different surgical techniques have been developed to reduce the duration of ischaemia and this includes the latest transluminal techniques. Severity of ischaemia can be minimised by the use of CSF drainage, hypothermia, partial bypass and the use of adjunctive pharmacological therapy. Reperfusion injury can be reduced with the use of anti-oxidant therapy. The aetiology of neurological complications after descending and thoracoabdominal aortic surgery has been well described and attempts have been made to minimise this incidence based on our knowledge of the pathophysiology of spinal cord ischaemia. However, our understanding of the development and prevention of these complications require further investigation in the clinical setting before surgery on descending and thoracoabdominal aorta to be performed with negligible occurrence of these disabling neurological problems.