| Added by | standudu |
|---|---|
| Group name | EquipeCTCS |
| 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 | C. Chevalier |
| Author | G. Collin |
| Author | S. Descamps |
| Author | H. Touaitahuata |
| Author | V. Simon |
| Author | N. Reymond |
| Author | L. Fernandez |
| Author | P. E. Milhiet |
| Author | V. Georget |
| Author | S. Urbach |
| Author | L. Lasorsa |
| Author | B. Orsetti |
| Author | F. Boissiere-Michot |
| Author | E. Lopez-Crapez |
| Author | C. Theillet |
| Author | S. Roche |
| Author | C. 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 | 2016 |
| Journal Abbr | Nat Commun |
| DOI | 10.1038/ncomms10765 |
| ISSN | 2041-1723 (Electronic) 2041-1723 (Linking) |
| Tags | original |
| Date Added | 2018/11/14 - 15:25:02 |
| Date Modified | 2019/05/31 - 13:09:32 |
| Notes and Attachments | (Note) (Note) 26899482 (Attachment) |
Institut de Recherche en Cancérologie de
