A Rationally Designed Peptide " Super

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Transcript A Rationally Designed Peptide " Super

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
Experimental design
VGLL4 is a potential
tumor suppressor
Function Study
How does VGLL4 function?
Mechanism Study
Key residues for
VGLL4-TEAD4 complex
formation?
A Rationally Designed Peptide
“Super-TDU”
2015/4/7
Structural Study
Clinical Study
Result 1:
2015/4/7
VGLL4 Is a Potential Tumor Suppressor
in Human Gastric Cancer
Result 2:
2015/4/7
VGLL4 Suppresses GC Growth in Vitro by
Targeting YAP-TEADs
Result 3:
2015/4/7
VGLL4 Functions through Competing with
YAP for TEAD4 Binding
Result 4:
2015/4/7
TDU Domains Alone Are Sufficient for VGLL4
Function of Inhibiting YAP
Structural Study
Result 5:
2015/4/7
A Rationally Designed Peptide " Super-TDU "
Potently Inhibits GC Growth
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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Magness, S.T., Smits, R., Ogino, S., et al. (2013). Restriction of intestinal stem cell
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