Abstract LB106: The EGF domains of MUC4 ...
Document type :
Autre communication scientifique (congrès sans actes - poster - séminaire...)
Title :
Abstract LB106: The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets
Author(s) :
Stoup, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Schulz, Céline [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Vasseur, Romain [Auteur]
Université Lille Nord (France)
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Magnez, Romain [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Thuru, Xavier [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Renault, Nicolas [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Jonckheere, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Lebegue, Nicolas [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Van Seuningen, Isabelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Schulz, Céline [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Vasseur, Romain [Auteur]
Université Lille Nord (France)
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Magnez, Romain [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Thuru, Xavier [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Renault, Nicolas [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Institut de Chimie Pharmaceutique Albert Lespagnol [ICPAL]
Jonckheere, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Lebegue, Nicolas [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Van Seuningen, Isabelle [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Conference title :
AACR Annual Meeting 2021
City :
Philadelphia
Country :
Etats-Unis d'Amérique
Start date of the conference :
2021
Publication date :
2021-07-01
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract The MUC4 mucin and its membrane partner ErbB2 form an oncogenic complex at the surface of epithelial cancer cells that promotes tumor progression. They directly physically interact via an extracellular region of ...
Show more >Abstract The MUC4 mucin and its membrane partner ErbB2 form an oncogenic complex at the surface of epithelial cancer cells that promotes tumor progression. They directly physically interact via an extracellular region of MUC4 encompassing three EGF domains opening the route to therapeutic targeting of ErbB2 over-expressing cancers in which MUC4-ErbB2 is present. However, before small inhibitory molecules may be designed, it is mandatory (i) to decipher at the molecular level which amino acid regions are involved in the interaction and (ii) show that they mediate cancer cell tumorigenicity. By using in vitro (2D cell culture, Micro Scale Thermophoresis, PLA assay, Co-IP, GST pull down, Molecular Dynamics simulations) and in vivo (xenograft model of pancreatic cancer) approaches, we show that the EGF1 domain of MUC4 is central both in the interaction with ErbB2 and in the activation of cell proliferation and migration and tumor growth via activation of key oncogenic pathways (Src, Ras, p70S6K/AKT/mTOR, β-catenin, FAK). Finally, we have identified hotspots of interaction paving the way to the design of therapeutic inhibitory molecules targeting the EGF domains of MUC4 which may represent a new alternative strategy to overcome ErbB2 therapeutic failure in cancer. Citation Format: Nicolas STOUP, Maxime LIBERELLE, Céline SCHULZ, Romain VASSEUR, Romain MAGNEZ, Xavier THURU, Patricia MELNYK, Nicolas RENAULT, Nicolas JONCKHEERE, Nicolas LEBEGUE, Isabelle VAN SEUNINGEN. The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB106.Show less >
Show more >Abstract The MUC4 mucin and its membrane partner ErbB2 form an oncogenic complex at the surface of epithelial cancer cells that promotes tumor progression. They directly physically interact via an extracellular region of MUC4 encompassing three EGF domains opening the route to therapeutic targeting of ErbB2 over-expressing cancers in which MUC4-ErbB2 is present. However, before small inhibitory molecules may be designed, it is mandatory (i) to decipher at the molecular level which amino acid regions are involved in the interaction and (ii) show that they mediate cancer cell tumorigenicity. By using in vitro (2D cell culture, Micro Scale Thermophoresis, PLA assay, Co-IP, GST pull down, Molecular Dynamics simulations) and in vivo (xenograft model of pancreatic cancer) approaches, we show that the EGF1 domain of MUC4 is central both in the interaction with ErbB2 and in the activation of cell proliferation and migration and tumor growth via activation of key oncogenic pathways (Src, Ras, p70S6K/AKT/mTOR, β-catenin, FAK). Finally, we have identified hotspots of interaction paving the way to the design of therapeutic inhibitory molecules targeting the EGF domains of MUC4 which may represent a new alternative strategy to overcome ErbB2 therapeutic failure in cancer. Citation Format: Nicolas STOUP, Maxime LIBERELLE, Céline SCHULZ, Romain VASSEUR, Romain MAGNEZ, Xavier THURU, Patricia MELNYK, Nicolas RENAULT, Nicolas JONCKHEERE, Nicolas LEBEGUE, Isabelle VAN SEUNINGEN. The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB106.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Collections :
Source :