| Added by | standudu |
|---|---|
| Group name | EquipeAT |
| Item Type | Journal Article |
| Title | The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation |
| Creator | Le Clorennec et al. |
| Author | Christophe Le Clorennec |
| Author | Yassamine Lazrek |
| Author | Olivier Dubreuil |
| Author | Christel Larbouret |
| Author | Marie-Alix Poul |
| Author | Philippe Mondon |
| Author | Gerry Melino |
| Author | André Pèlegrin |
| Author | Thierry Chardès |
| Abstract | We characterized the mechanism of action of the neuregulin-non-competitive anti-HER3 therapeutic antibody 9F7-F11 that blocks the PI3K/AKT pathway, leading to cell cycle arrest and apoptosis in vitro and regression of pancreatic and breast cancer in vivo. We found that 9F7-F11 induces rapid HER3 down-regulation. Specifically, 9F7-F11-induced HER3 ubiquitination and degradation in pancreatic, breast and prostate cancer cell lines was driven mainly by the itchy E3 ubiquitin ligase (ITCH/AIP4). Overexpression of the ITCH/AIP4 inhibitor N4BP1 or small-interfering RNA-mediated knockdown of ITCH/AIP4 inhibited HER3 ubiquitination/degradation and PI3K/AKT signaling blockade induced by 9F7-F11. Moreover, 9F7-F11-mediated JNK1/2 phosphorylation led to ITCH/AIP4 activation and recruitment to HER3 for receptor ubiquitination and degradation. ITCH/AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference. Taken together, our results suggest that 9F7-F11-induced HER3 ubiquitination and degradation in cancer cells mainly occurs through JNK1/2-dependent ITCH/AIP4 activation. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 24 |
| Pages | 37013-37029 |
| Date | Jun 14, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.9455 |
| ISSN | 1949-2553 |
| Library Catalog | PubMed |
| Extra | PMID: 27203743 PMCID: PMC5095055 |
| Tags | Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, antibody, Antineoplastic Agents, cancer, Cell Line, Tumor, Down-Regulation, HER3, Humans, ITCH/AIP4, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinase 9, original, Receptor, ErbB-3, Repressor Proteins, Ubiquitin-Protein Ligases, Ubiquitination |
| Date Added | 2019/05/29 - 16:11:13 |
| Date Modified | 2019/05/29 - 16:11:28 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
