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A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer

A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer. Feng Junnan. Cancer Cell 25, 166–180, February 10, 2014. Introduction. Function Study. M echanism Study. Structural Study. Clinical Study. Experimental design. VGLL4 i s a p otential

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A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer

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  1. A Peptide Mimicking VGLL4 Function Actsas a YAP Antagonist Therapy against Gastric Cancer Feng Junnan Cancer Cell 25, 166–180, February 10, 2014

  2. Introduction

  3. Function Study Mechanism Study Structural Study Clinical Study Experimental design VGLL4 is a potential tumor suppressor How does VGLL4 function? Key residues for VGLL4-TEAD4 complex formation? A Rationally Designed Peptide “Super-TDU” 2014/8/21

  4. Result 1： VGLL4 Is a Potential Tumor Suppressor in Human Gastric Cancer 2014/8/21

  5. Result 2： VGLL4 Suppresses GC Growth in Vitro by Targeting YAP-TEADs 2014/8/21

  6. Result 3： VGLL4 Functions through Competing with YAP for TEAD4 Binding 2014/8/21

  7. Result 4： TDU Domains Alone Are Sufficient for VGLL4 Function of Inhibiting YAP 2014/8/21

  8. Structural Study

  9. Result 5： A Rationally Designed Peptide " Super-TDU " Potently Inhibits GC Growth 2014/8/21

  10. 1、Inhibits GC Growth

  11. 2、Pharmacological Evaluation of the Super-TDU

  12. 3、Inhibits Tumor Growth of Human Primary GC

  13. 4、 Inhibits GC Tumor Growth in the H. pylori-Infected Mouse Model

  14. summary Super--TDU cancer cell overactive YAP

  15. Gains • Important signal pathway-- Hippo • Novel therapy against cancer -- Physical antagonist • Simple technologies , rigorous design.

  16. References • Avruch, J., Zhou, D., and Bardeesy, N. (2012). YAP oncogene overexpressionsupercharges colon cancer proliferation. Cell Cycle11, 1090–1096. • Azzolin, L., Zanconato, F., Bresolin, S., Forcato, M., Basso, G., Bicciato, S.,Cordenonsi, M., and Piccolo, S. (2012). Role of TAZ as mediator of Wntsignaling. Cell151, 1443–1456. • Barry, E.R., Morikawa, T., Butler, B.L., Shrestha, K., de la Rosa, R., Yan, K.S.,Fuchs, .S., Magness, S.T., Smits, R., Ogino, S., et al. (2013). Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature493, 106–110. • Cai, J., Zhang, N., Zheng, Y., de Wilde, R.F., Maitra, A., and Pan, D. (2010). TheHippo ignaling pathway restricts the oncogenic potential of an intestinalregeneration program. Genes Dev.24, 2383–2388. • Chan, S.W., Lim, C.J., Chen, L., Chong, Y.F., Huang, C., Song, H., and Hong,W. (2011). The Hippo pathway in biological control and cancer development.J. Cell. Physiol.226, 928–939.

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