Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes
Version of Record online: 11 OCT 2013
Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO
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EMBO Molecular Medicine
Volume 5, Issue 11, pages 1720–1739, November 2013
How to Cite
Yoon, J.-H., Jung, S. M., Park, S. H., Kato, M., Yamashita, T., Lee, I.-K., Sudo, K., Nakae, S., Han, J. S., Kim, O.-H., Oh, B.-C., Sumida, T., Kuroda, M., Ju, J.-H., Jung, K. C., Park, S. H., Kim, D.-K. and Mamura, M. (2013), Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med, 5: 1720–1739. doi: 10.1002/emmm.201302524
- Issue online: 4 NOV 2013
- Version of Record online: 11 OCT 2013
- Manuscript Accepted: 6 SEP 2013
- Manuscript Revised: 25 AUG 2013
- Manuscript Received: 24 JAN 2013
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Association for Preventive Medicine of Japan, Bio Technology R&D Program, Republic of Korea. Grant Number: 20090081756
- National Research Foundation of Korea
- Ministry of Education, Science and Technology of Korea. Grant Number: R32-10064
- Ministry of Education, Science and Technology, Korea. Grant Number: 20100029596
- Basic Science Research Program through the National Research Foundation of Korea. Grant Number: 2012R1A1A3015334
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Figure S1. Detection of lymph node metastsis.
Figure S2. TGF-β does not affect apoptosis and cell cycle of B16 cells.
Figure S3. Oral administration of EW-7197 suppresses melanoma and LN metastases with enhanced CTL activity.
Figure S4. Oral administration of EW-7197 inhibits TGF-β signalling and downregulates Smad4 in spleen cells of melanoma-bearing mice.
Figure S5. Oral administration of LY-2157299 inhibits TGF-β signalling and downregulates Smad4 in dLN cells of melanoma-bearing mice.
Figure S6. LY-2157299 induces Smad4 ubiquitination in dLN cells of melanoma-bearing mice.
Figure S7. R-Smads are not ubiquitinated in dLN cells of EW-7197-treated melanoma-bearing mice.
Figure S8. Smurf1 and Smurf2 are not involved in degradation of Smad4 by ALK5 inhibition.
Figure S9. T-cell-specific Smad4 deletion suppresses melanoma and LN metastases with enhanced CTL activity.
Figure S10. Upregulation of Eomes in CD8+ T cells by ALK5 inibition or T-cell-specific Smad4 deletion.
Figure S11. Eomes is not expressed in CD4+ cells in the dLNs of melanoma-bearing mice.
Figure S12. Characterization of TILs.
Figure S13. Deletion of CD8+ T cells, CD4+ T cells, NK cells in vivo.
Figure S14. T-cell-specific Smad4 deletion.
Figure S15. Effect of Smad4 on PMA/ionomycin-stimulated CD8+ T cells.
Table S1. Primer sequences for quantitative RT-PCR.
Table S2. Primer sequences for the proximal promoter regions of Eomes.
Table S3. Primer sequences for ChIP.
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