4 results on '"Maia Chanrion"'
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2. Reciprocal interaction of Wnt and RXR-α pathways in hepatocyte development and hepatocellular carcinoma.
- Author
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Jinyu Li, Maia Chanrion, Eric Sawey, Tim Wang, Edward Chow, Aaron Tward, Yi Su, Wen Xue, Robert Lucito, Lars Zender, Scott W Lowe, J Michael Bishop, and Scott Powers
- Subjects
Medicine ,Science - Abstract
Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal development. We found a major shift in expression of Wnt and RXR-α pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-α gene signature categorized HCCs into two subtypes (high Wnt, low RXR-α and low Wnt, high RXR-α), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-α levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-α achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-α, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target.
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- 2015
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3. Identification of a Therapeutic Strategy Targeting Amplified FGF19 in Liver Cancer by Oncogenomic Screening
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Chunlin Cai, Scott W. Lowe, Eric T. Sawey, Scott Powers, Ronald W. Busuttil, Alice Zhao, Herman Yee, Lars Zender, Lincoln Stein, Dorothy French, Guanming Wu, Maia Chanrion, Richard S. Finn, and Jianping Zhang
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Cancer Research ,Carcinoma, Hepatocellular ,Immunoblotting ,Mice, Nude ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Gene duplication ,medicine ,Animals ,Humans ,Cyclin D1 ,Genetic Predisposition to Disease ,neoplasms ,Cell Proliferation ,030304 developmental biology ,Oncogene Proteins ,0303 health sciences ,Gene knockdown ,Oncogene ,Chromosomes, Human, Pair 11 ,Liver Neoplasms ,Gene Amplification ,Antibodies, Monoclonal ,Cancer ,Genomics ,Cell Biology ,Amplicon ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular biology ,digestive system diseases ,Tumor Burden ,3. Good health ,Fibroblast Growth Factors ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,Biomarker (medicine) ,Female ,RNA Interference ,Liver cancer - Abstract
SummaryWe screened 124 genes that are amplified in human hepatocellular carcinoma (HCC) using a mouse hepatoblast model and identified 18 tumor-promoting genes, including CCND1 and its neighbor on 11q13.3, FGF19. Although it is widely assumed that CCND1 is the main driving oncogene of this common amplicon (15% frequency in HCC), both forward-transformation assays and RNAi-mediated inhibition in human HCC cells established that FGF19 is an equally important driver gene in HCC. Furthermore, clonal growth and tumorigenicity of HCC cells harboring the 11q13.3 amplicon were selectively inhibited by RNAi-mediated knockdown of CCND1 or FGF19, as well as by an anti-FGF19 antibody. These results show that 11q13.3 amplification could be an effective biomarker for patients most likely to respond to anti-FGF19 therapy.
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- 2011
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4. Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut
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Elodie Girard, Emmanuel Barillot, Perrine Paul-Gilloteaux, Silvia Fre, Silvina Dos Reis Tavares, David P. A. Cohen, Maia Chanrion, Andrei Zinovyev, Luc Fetler, Lev Stimmer, Ivan Bièche, Patricia Legoix-Né, Cédric Barrière, Danijela Matic Vignjevic, Sylvie Robine, Inna Kuperstein, Loredana Martignetti, Daniel Louvard, Giuseppe-Fulvio Boccia, Didier Meseure, Fatima El Marjou, Wulfran Cacheux, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Facultés des sciences pharmaceutiques et biologiques, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Platform of Investigative Pathology, Institut Curie [Paris], Physico-Chimie-Curie (PCC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Service de Bioinformatique (CURIE-BIOINFO), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
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Genetically modified mouse ,Epithelial-Mesenchymal Transition ,Genotype ,[SDV]Life Sciences [q-bio] ,Transgene ,Green Fluorescent Proteins ,Molecular Sequence Data ,General Physics and Astronomy ,Mice, Transgenic ,Biology ,Bioinformatics ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Mice ,In vivo ,Image Processing, Computer-Assisted ,medicine ,Animals ,Humans ,Cell Lineage ,Exome ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,Receptor, Notch1 ,DNA Primers ,Multidisciplinary ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Mesenchymal stem cell ,Sequence Analysis, DNA ,General Chemistry ,medicine.disease ,Immunohistochemistry ,Epithelium ,Gastrointestinal Tract ,Disease Models, Animal ,medicine.anatomical_structure ,Cancer research ,Tumor Suppressor Protein p53 ,Signal transduction ,Signal Transduction - Abstract
Epithelial-to-mesenchymal transition-like (EMT-like) is a critical process allowing initiation of metastases during tumour progression. Here, to investigate its role in intestinal cancer, we combine computational network-based and experimental approaches to create a mouse model with high metastatic potential. Construction and analysis of this network map depicting molecular mechanisms of EMT regulation based on the literature suggests that Notch activation and p53 deletion have a synergistic effect in activating EMT-like processes. To confirm this prediction, we generate transgenic mice by conditionally activating the Notch1 receptor and deleting p53 in the digestive epithelium (NICD/p53−/−). These mice develop metastatic tumours with high penetrance. Using GFP lineage tracing, we identify single malignant cells with mesenchymal features in primary and metastatic tumours in vivo. The development of such a model that recapitulates the cellular features observed in invasive human colorectal tumours is appealing for innovative drug discovery., Metastasizing tumour cells undergo epithelial-to-mesenchymal transition. Using both bioinformatic and in vivo approaches, Chanrion et al. identify combined Notch activation and p53 inactivation as a potent inducer of this transition, and apply this to create a highly metastatic tumour model in mice.
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- 2014
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