| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion |
| Creator | Chevalier et al. |
| Author | Clément Chevalier |
| Author | Guillaume Collin |
| Author | Simon Descamps |
| Author | Heiani Touaitahuata |
| Author | Valérie Simon |
| Author | Nicolas Reymond |
| Author | Laurent Fernandez |
| Author | Pierre-Emmanuel Milhiet |
| Author | Virginie Georget |
| Author | Serge Urbach |
| Author | Laurence Lasorsa |
| Author | Béatrice Orsetti |
| Author | Florence Boissière-Michot |
| Author | Evelyne Lopez-Crapez |
| Author | Charles Theillet |
| Author | Serge Roche |
| Author | Christine Benistant |
| Abstract | ERBB2 overexpression in human breast cancer leads to invasive carcinoma but the mechanism is not clearly understood. Here we report that TOM1L1 is co-amplified with ERBB2 and defines a subgroup of HER2(+)/ER(+) tumours with early metastatic relapse. TOM1L1 encodes a GAT domain-containing trafficking protein and is a SRC substrate that negatively regulates tyrosine kinase signalling. We demonstrate that TOM1L1 upregulation enhances the invasiveness of ERBB2-transformed cells. This pro-tumoural function does not involve SRC, but implicates membrane-bound membrane-type 1 MMP (MT1-MMP)-dependent activation of invadopodia, membrane protrusions specialized in extracellular matrix degradation. Mechanistically, ERBB2 elicits the indirect phosphorylation of TOM1L1 on Ser321. The phosphorylation event promotes GAT-dependent association of TOM1L1 with the sorting protein TOLLIP and trafficking of the metalloprotease MT1-MMP from endocytic compartments to invadopodia for tumour cell invasion. Collectively, these results show that TOM1L1 is an important element of an ERBB2-driven proteolytic invasive programme and that TOM1L1 amplification potentially enhances the metastatic progression of ERBB2-positive breast cancers. |
| Publication | Nature Communications |
| Volume | 7 |
| Pages | 10765 |
| Date | Feb 22, 2016 |
| Journal Abbr | Nat Commun |
| Language | eng |
| DOI | 10.1038/ncomms10765 |
| ISSN | 2041-1723 |
| Library Catalog | PubMed |
| Extra | PMID: 26899482 PMCID: PMC4764922 |
| Tags | 3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Breast Neoplasms, Carcinoma, Ductal, Breast, Cell Line, Tumor, Female, Humans, Intracellular Signaling Peptides and Proteins, Matrix Metalloproteinase 14, Mice, Neoplasm Invasiveness, original, Receptor, ErbB-2 |
| Date Added | 2018/11/13 - 17:26:12 |
| Date Modified | 2019/05/21 - 14:43:12 |
Institut de Recherche en Cancérologie de
