Today we would like to highlight the study of Dr Nicolas Lebègue and his co-workers from university of Lille.
A feature of pancreatic cancer is the frequent overexpression of receptor HER2 along with its membrane partner the MUC4 oncomucin in the early stages of the pancreatic carcinogenesis. However, therapeutic approaches targeting HER2 in pancreatic cancer are not efficient so far.
We are glad to have contributed to this study that aimed at investigating the EGF domains of MUC4 Oncomucin which mediate HER2, in search of new therapeutics pathways.
In order to study the interaction of MUC4 and HER2 involving the EGF domains, we were asked to create vectors lacking the EGF1 or EGF2 domains as well as others lacking the transmembrane and / or cytoplasmic domain of MUC4.
As the results show, EGF domains play a major role in the MUC4 and HER2 interaction, indeed without the presence of EGF domains, cells migrations and proliferations are reduced
This study show how that EGF domains of MUC4 may be important for cancer progression, highlighting their potential as new molecular target for therapeutic strategies to be developed.
Figure 1: eGFP‐MUC4 fusion proteins with EGF1 and EGF2 deletion domain mutants.
Figure 2: Impact of deletion of MUC4(EGF1) and MUC4(EGF2) domains on binding affinities with HER2 and on proliferation and migration properties of human PC cells.
Article and figure: The EGF Domains of MUC4 Oncomucin Mediate HER2 Binding Affinity and Promote Pancreatic Cancer Cell Tumorigenesis!
Nicolas Stoup, Maxime Liberelle,Céline Schulz Sumeyye Cavdarli ,Romain Vasseur ,Romain Magnez ,Fatima Lahdaoui Nicolas Skrypek Fabien Peretti, Frédéric Frénois Xavier Thuru Patricia Melnyk ,Nicolas Renault Nicolas Jonckheere Nicolas Lebègue Isabelle Van Seuningen