title: p63/MT1-MMP axis is required for in situ to invasive transition in basal-like breast cancer.
abstract: The transition of ductal carcinoma in situ (DCIS) to invasive breast carcinoma requires tumor cells to cross the basement membrane (BM). However, mechanisms underlying BM transmigration are poorly understood. Here, we report that expression of membrane-type 1 (MT1)-matrix metalloproteinase (MMP), a key component of the BM invasion program, increases during breast cancer progression at the in situ to invasive breast carcinoma transition. In the intraductal xenograft model, MT1-MMP is required for BM transmigration of MCF10DCIS.com breast adenocarcinoma cells and is overexpressed in cell clusters overlying focal BM disruptions and at the invasive tumor front. Mirrored upregulation of p63 and MT1-MMP is observed at the edge of MCF10DCIS.com xenograft tumors and p63 is required for induction of MT1-MMP-dependent invasive program in response to microenvironmental signals. Immunohistochemistry and analysis of public database reveal that p63 and MT1-MMP are upregulated in human basal-like breast tumors suggesting that p63/MT1-MMP axis contributes to progression of basal-like breast cancers with elevated p63 and MT1-MMP levels.
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lodillinsky
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Infante
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Guichard
authors.affiliation: Mammalian Developmental Epigenetics Group, Genetics and Developmental Biology Unit, Institut Curie, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Chaligné
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Fuhrmann
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Cyrta
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Irondelle
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Lagoutte
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Vacher
authors.affiliation: RT2Lab Team, Translational Research Department, Institut Curie, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Bonsang-Kitzis
authors.affiliation: Molecular Mechanisms of Mammary Gland Development Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Glukhova
authors.affiliation: RT2Lab Team, Translational Research Department, Institut Curie, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Reyal
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Bièche
authors.affiliation: Mammalian Developmental Epigenetics Group, Genetics and Developmental Biology Unit, Institut Curie, Paris, France.|Pathology Department, Institut Curie, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Vincent-Salomon
authors.affiliation: Membrane and Cytoskeleton Dynamics Group, Cell Dynamics and Compartmentalization Unit, Institut Curie, Centre National de la Recherche Scientifique UMR144, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020781:Matrix Metalloproteinase 1