Skip to Main content Skip to Navigation
Journal articles

TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion

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
Complete list of metadata
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Tuesday, June 8, 2021 - 2:24:24 PM
Last modification on : Friday, December 10, 2021 - 4:08:34 PM
Long-term archiving on: : Thursday, September 9, 2021 - 7:29:42 PM


Publisher files allowed on an open archive


Distributed under a Creative Commons Attribution 4.0 International License



Clément Chevalier, Guillaume Collin, Simon Descamps, Heiani Touaitahuata, Valérie Simon, et al.. TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion. Nature Communications, Nature Publishing Group, 2016, 7 (1), pp.10765. ⟨10.1038/ncomms10765⟩. ⟨hal-01299292⟩



Les métriques sont temporairement indisponibles