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 PowerPoint PPT Presentation


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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 Actsas a YAP Antagonist Therapy against Gastric Cancer

Feng Junnan

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


Introduction


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


Result 1:

VGLL4 Is a Potential Tumor Suppressor in Human Gastric Cancer

2014/8/21


Result 2:

VGLL4 Suppresses GC Growth in Vitro by Targeting YAP-TEADs

2014/8/21


Result 3:

VGLL4 Functions through Competing with YAP for TEAD4 Binding

2014/8/21


Result 4:

TDU Domains Alone Are Sufficient for VGLL4 Function of Inhibiting YAP

2014/8/21


Structural Study


Result 5:

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

2014/8/21


1、Inhibits GC Growth


2、Pharmacological Evaluation of the Super-TDU


3、Inhibits Tumor Growth of Human Primary GC


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


summary

Super--TDU

cancer cell

overactive YAP


Gains

  • Important signal pathway-- Hippo

  • Novel therapy against cancer -- Physical antagonist

  • Simple technologies , rigorous design.


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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