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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 - PowerPoint PPT Presentation
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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
23/4/22
Experimental designVGLL4 is a potential
tumor suppressor
How does VGLL4 function?
Key residues for VGLL4-TEAD4 complex formatio
n?
A Rationally Designed Peptide “Super-TDU”
Structural Study
Function Study
Mechanism Study
Clinical Study
23/4/22
VGLL4 Is a Potential Tumor Suppressor in Human Gastric Cancer
Result 1：
23/4/22
VGLL4 Suppresses GC Growth in Vitro by Targeting YAP-TEADs
Result 2：
23/4/22
VGLL4 Functions through Competing with YAP for TEAD4 Binding
Result 3：
23/4/22
TDU Domains Alone Are Sufficient for VGLL4 Function of Inhibiting YAP
Result 4：
Structural Study
23/4/22
A Rationally Designed Peptide " Super-TDU " Potently Inhibits GC Growth
Result 5：
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
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• 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. Nature 493, 106–110.
• Cai, J., Zhang, N., Zheng, Y., de Wilde, R.F., Maitra, A., and Pan, D. (2010). The Hippo ignaling pathway restricts the oncogenic potential of an intestinal regeneration 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.
