[PubMed] [Google Scholar] 12. results indicate that CLIC1 is an important contributor to tumor invasion, metastasis and angiogenesis. Implications This study uncovers an important new function of CLIC1 in the regulation of cell-extracellular matrix interactions and ability of tumor cells to metastasize to distant organs. results, we found that knockdown of CLIC1 significantly reduced experimental lung metastasis, suggesting that CLIC1-mediated functions are necessary alpha-Boswellic acid for efficient tumor cell seeding in the lungs. Together, these results show that fibrin-embedded tumor and endothelial cells depend on CLIC1 for invadopodia and colony formation and lung metastasis and that this function correlates with the capacity of CLIC1 to promote lung metastasis and to metastasize to distant organs in vivo. Thus, strategies to inhibit CLIC1 could be useful for the treatment of aggressive cancer. Supplementary Material 1Click here to view.(186K, pdf) ACKNOWLEDGEMENTS We would like to thank Dr. Robert Sobol and Ashley Brown from the UPCI Vector Core Facility for constructing shRNA vectors. This project used the UPCI Cell and Tissue Imaging Facility, UPCI Animal Facility and the UPCI Vector Core Facility, which are supported by the UPCI Cancer Center Support Grant. GRANT alpha-Boswellic acid SUPPORT This work was supported by National Institutes of Health grants CA134330 (JP), 5T32DK007774-14 (LAG), and P30CA047904 (UPCI alpha-Boswellic acid CCSG). Footnotes The authors have no potential conflict of interest. REFERENCES 1. Millien VO, Lu W, Shaw J, Yuan X, Mak G, Roberts L, et al. Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science. 2013;341:792C796. [PMC free article] [PubMed] [Google Scholar] 2. van den Berg YW, van den Hengel LG, Myers HR, Ayachi O, Jordanova E, Ruf W, et al. 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