01 or <0.001 was indicated as *, ** or *** respectively. Figure 4 Shh/Gli signaling down-regulates E-Cadherin expression. Immunofluorescent staining of E-Cad (green) in lung SCC H2170 cells treated with Gli-I,

vismodegib, and recombinant Shh proteins. DAPI (blue) was used to stain nuclei of those cells. Conclusions Our study provides evidence for aberrant activation find more of Shh/Gli pathway and a strong association between expressions of Gli proteins and EMT markers in human lung SCC, as well as the implication of activated Shh/Gli pathway in cell migration and EMT process. Our findings suggest that the Shh/Gli pathway may be a critical component in lung SCC recurrence, metastasis and resistance to chemotherapy. Inhibition of the Shh/Gli pathway activity/function is a potential therapeutic strategy for the treatment of lung SCC patients. Acknowledgements BTK inhibitor concentration This work was supported by NIH/NCI R01CA125030, and the Eileen D. Ludwig Endowed for Thoracic Oncology Research (to B He); The Bonnie J. Addario Lung Cancer Foundation, the Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley & Oberman Foundation, the Ziegelmam Family Foundation, and the Barbara Isackson Lung Cancer Research Fund (to DM Jablons); Tianjin Municipal Science and Technology Commission (12JCYBJC17800)

and the Key Program for Anti-cancer Research of Tianjin Municipal Science and Technology Commission (12ZCDZSY15400) (to CL Wang). References 1. Siegel R, Ma JM, Zou ZH, Jemal A: Cancer statistics. CA Cancer J Clin 2014, 64:9–29.PubMedCrossRef Tau-protein kinase 2. Travis WD: Pathology of lung cancer. Clin Chest Med 2012, 32:669.CrossRef 3. Drilon A, Rekhtman N, Ladanyi M, Paik P: Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol 2012, 13:E418-E426.PubMedCrossRef 4. Little AG, Gay EG, Gaspar LE, Stewart AK: National survey of non-small cell lung cancer in the United States:

Epidemiology, pathology and patterns of care. Lung Cancer 2007, 57:253–260.PubMedCrossRef 5. de Craene B, Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013, 13:97–110.PubMedCrossRef 6. Hong KO, Kim JH, Hong JS, Yoon HJ, Lee JI, Hong SP, Hong SD: Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells. J Exp Clin Cancer Res 2009, 28:28–38.PubMedCentralPubMedCrossRef 7. Soltermann A, Tischler V, Arbogast S, Braun J, Probst-Hensch N, Weder W, Moch H, Kristiansen G: Prognostic significance of epithelial-mesenchymal and selleck mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res 2008, 14:7430–7437.PubMedCrossRef 8. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ: Direct regulation of TWIST by HIF-1 alpha promotes metastasis. Nat Cell Biol 2008, 10:295–305.PubMedCrossRef 9.