A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer
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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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A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer

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

Feng Junnan

Cancer Cell 25, 166–180, February 10, 2014


Introduction

Introduction


Experimental design

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


Vgll4 is a potential tumor suppressor in human gastric cancer

Result 1:

VGLL4 Is a Potential Tumor Suppressor in Human Gastric Cancer

2014/8/21


Vgll4 suppresses gc growth in vitro by targeting yap teads

Result 2:

VGLL4 Suppresses GC Growth in Vitro by Targeting YAP-TEADs

2014/8/21


Vgll4 functions through competing with yap for tead4 binding

Result 3:

VGLL4 Functions through Competing with YAP for TEAD4 Binding

2014/8/21


Tdu domains alone are sufficient for vgll4 function of inhibiting yap

Result 4:

TDU Domains Alone Are Sufficient for VGLL4 Function of Inhibiting YAP

2014/8/21


Structural study

Structural Study


A rationally designed peptide super tdu potently inhibits gc growth

Result 5:

A Rationally Designed Peptide " Super-TDU " Potently Inhibits GC Growth

2014/8/21


A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer

1、Inhibits GC Growth


A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer

2、Pharmacological Evaluation of the Super-TDU


A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer

3、Inhibits Tumor Growth of Human Primary GC


A peptide mimicking vgll4 function acts as a yap antagonist therapy against gastric cancer

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


Summary

summary

Super--TDU

cancer cell

overactive YAP


Gains

Gains

  • Important signal pathway-- Hippo

  • Novel therapy against cancer -- Physical antagonist

  • Simple technologies , rigorous design.


References

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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