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

Autor: Béatrice Orsetti, Virginie Georget, Christine Benistant, Guillaume Collin, Heiani Touaitahuata, Laurent Fernandez, Charles Theillet, Simon Descamps, Pierre-Emmanuel Milhiet, Florence Boissière-Michot, Evelyne Lopez-Crapez, Serge Roche, Clément Chevalier, Nicolas Reymond, Serge Urbach, Laurence Lasorsa, Valérie Simon
Přispěvatelé: Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Microscopie de Rennes (MRic), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'anatomo-pathologie, CRLCC Val d'Aurelle - Paul Lamarque, Département d'oncologie Médicale, Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Jonchère, Laurent, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Ligue Nationnale Contre le Cancer, Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Receptor
ErbB-2
[SDV]Life Sciences [q-bio]
Science
Endocytic cycle
General Physics and Astronomy
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
macromolecular substances
Biology
General Biochemistry
Genetics and Molecular Biology
SH3 domain
Article
03 medical and health sciences
Mice
Downregulation and upregulation
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line
Tumor
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Matrix Metalloproteinase 14
Animals
Humans
Neoplasm Invasiveness
skin and connective tissue diseases
neoplasms
Adaptor Proteins
Signal Transducing
Cancer
Multidisciplinary
TOLLIP
Carcinoma
Ductal
Breast
Intracellular Signaling Peptides and Proteins
General Chemistry
3T3 Cells
Cell Biology
3. Good health
Cell biology
Biological sciences
030104 developmental biology
Invadopodia
Phosphorylation
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Female
Tyrosine kinase
Proto-oncogene tyrosine-protein kinase Src
Zdroj: Nature Communications, Vol 7, Iss 1, Pp 1-16 (2016)
Nature Communications
Nature Communications, 2016, 7 (1), pp.10765. ⟨10.1038/ncomms10765⟩
Nature Communications, Nature Publishing Group, 2016, 7 (1), pp.10765. ⟨10.1038/ncomms10765⟩
ISSN: 2041-1723
DOI: 10.1038/ncomms10765⟩
Popis: 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.
ERBB2 overexpression in human breast cancer leads to invasion and metastasis. Here the authors report that ERBB2 induces indirect phosphorylation of TOM1L1 that promotes trafficking of the metalloprotease MT1-MMP to invadopodia, which leads to tumour cell invasion.
Databáze: OpenAIRE
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