ETV4 transcription factor and MMP13 metalloprotease are interplaying actors of breast tumorigenesis

Autor: Dumortier, Mandy, Ladam, Franck, Damour, Isabelle, Vacher, Sophie, Bièche, Ivan, Marchand, Nathalie, De Launoit, Yvan, Tulasne, David, Chotteau-Lelièvre, Anne
Přispěvatelé: de Launoit, Yvan, Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Institut Curie [Paris], Institut de biologie de Lille - UMS 3702 (IBL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Centre national de la recherche scientifique (CNRS), the Institut Pasteur de Lille, and Institut National de la Santé et de la Recherche Médicale (INSERM), as well as by grants from the Ligue contre le Cancer, comité Aisne and the Association pour la Recherche sur le Cancer., We thank Martine Duterque-Coquillaud, Anne Flourens, and Antonino Bongiovanni for their precious help in IHC experiments. We thank the Microscopy-Imaging-Cytometry Facility of the BioImaging Center Lille Nord-de-France for access to instruments and technical advice., Mécanismes de tumorigenèse et thérapies ciblées, Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161 (M3T), Institut Curie, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Département de Génétique [Institut Curie, Paris] (Unité de Pharmacogénomique)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Carcinogenesis
[SDV]Life Sciences [q-bio]
Mice
Breast cancer
MESH: Aged
80 and over
Cell Movement
MESH: Animals
ComputingMilieux_MISCELLANEOUS
MESH: Breast Neoplasms/pathology
Aged
80 and over
MESH: Carcinogenesis/genetics
MESH: Aged
MESH: Middle Aged
MESH: Cell Movement/genetics
MMP13
MESH: Gene Expression Regulation
Neoplastic
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
MESH: Neoplasm Invasiveness/genetics
MESH: Breast Neoplasms/genetics
Gene Expression Regulation
Neoplastic
[SDV] Life Sciences [q-bio]
MESH: Proto-Oncogene Proteins/genetics
Female
Adenovirus E1A Proteins
MESH: Matrix Metalloproteinase 13/genetics
Research Article
Adult
MESH: Xenograft Model Antitumor Assays
MESH: Cell Line
Tumor
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
lcsh:RC254-282
MESH: Prognosis
Cell Line
Tumor
Proto-Oncogene Proteins
Matrix Metalloproteinase 13
Animals
Humans
Neoplasm Invasiveness
MESH: Mice
Aged
Cell Proliferation
MESH: Humans
Proto-Oncogene Proteins c-ets
ETV4
MESH: Cell Proliferation/genetics
MESH: Adult
Xenograft Model Antitumor Assays
Tumorigenesis
MESH: Adenovirus E1A Proteins/genetics
MESH: Neoplasm Invasiveness/pathology
Transcription factor
MESH: Female
Zdroj: Breast Cancer Research
Breast Cancer Research, 2018, 20 (1), pp.73. ⟨10.1186/s13058-018-0992-0⟩
Breast Cancer Research, BioMed Central, 2018, 20, ⟨10.1186/s13058-018-0992-0⟩
Breast Cancer Research, BioMed Central, 2018, 20 (1), pp.73. ⟨10.1186/s13058-018-0992-0⟩
Breast Cancer Research, Vol 20, Iss 1, Pp 1-18 (2018)
Breast Cancer Research : BCR
Breast Cancer Research, BioMed Central, 2018, 20 (1), ⟨10.1186/s13058-018-0992-0⟩
ISSN: 1465-5411
1465-542X
DOI: 10.1186/s13058-018-0992-0⟩
Popis: Background The ETS transcription factor ETV4 is involved in the main steps of organogenesis and is also a significant mediator of tumorigenesis and metastasis, such as in breast cancer. Indeed, ETV4 is overexpressed in breast tumors and is associated with distant metastasis and poor prognosis. However, the cellular and molecular events regulated by this factor are still misunderstood. In mammary epithelial cells, ETV4 controls the expression of many genes, MMP13 among them. The aim of this study was to understand the function of MMP13 during ETV4-driven tumorigenesis. Methods Different constructs of the MMP13 gene promoter were used to study the direct regulation of MMP13 by ETV4. Moreover, cell proliferation, migration, invasion, anchorage-independent growth, and in vivo tumorigenicity were assayed using models of mammary epithelial and cancer cells in which the expression of MMP13 and/or ETV4 is modulated. Importantly, the expression of MMP13 and ETV4 messenger RNA was characterized in 456 breast cancer samples. Results Our results revealed that ETV4 promotes proliferation, migration, invasion, and anchorage-independent growth of the MMT mouse mammary tumorigenic cell line. By investigating molecular events downstream of ETV4, we found that MMP13, an extracellular metalloprotease, was an ETV4 target gene. By overexpressing or repressing MMP13, we showed that this metalloprotease contributes to proliferation, migration, and anchorage-independent clonogenicity. Furthermore, we demonstrated that MMP13 inhibition disturbs proliferation, migration, and invasion induced by ETV4 and participates to ETV4-induced tumor formation in immunodeficient mice. Finally, ETV4 and MMP13 co-overexpression is associated with poor prognosis in breast cancer. Conclusion MMP13 potentiates the effects of the ETV4 oncogene during breast cancer genesis and progression. Electronic supplementary material The online version of this article (10.1186/s13058-018-0992-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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