title: Transcriptional signature induced by a metastasis-promoting c-Src mutant in a human breast cell line.
abstract: Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are found in the viral oncogene protein v-Src as well as in some advanced human colon cancers. They are associated with increased kinase activity and cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison with its wild-type protein, c-Src(wt), in the human non-transformed breast epithelial cell line MCF-10A. We demonstrated previously that the mutant altered migratory and metastatic properties. Genome-wide transcriptome analysis revealed that c-Src(mt) de-regulated the expression levels of approximately 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. 82.9% of these genes have previously been linked to cellular migration, while the others play roles in RNA transport and splicing processes, for instance. Consistent with the transcriptome data, cells expressing c-Src(mt), but not those expressing c-Src(wt), showed the capacity to metastasize into the lungs of mice in vivo. The mRNA expression profile of c-Src(mt)-expressing cells shows significant overlap with that of various primary human tumor samples, possibly reflecting elevated Src activity in some cancerous cells. Expression of c-Src(mt) led to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. These genes and pathways de-regulated by c-Src(mt) may provide suitable biomarkers or targets of therapeutic approaches for metastatic cells.
  
  
  
  This project was submitted to the National Center for Biotechnology Information BioProject under ID PRJNA288540. The Illumina RNA-Seq reads are available in the National Center for Biotechnology Information Sequence Read Archive under study ID SRP060008 with accession numbers SRS977414 for MCF-10A cells, SRS977717 for mock cells, SRS978053 for c-Src(wt) cells and SRS978046 for c-Src(mt) cells.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.|University of Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Broecker
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hardt
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Herwig
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Timmermann
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kerick
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wunderlich
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Michal R
authors.initials: MR
authors.lastname: Schweiger
authors.affiliation: Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: Lubor
authors.initials: L
authors.lastname: Borsig
authors.affiliation: Institute of Virology, Technische Universität München, Germany.|Institute of Virology, Helmholtz Zentrum Munich, Germany.|Department Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.|Dahlem Centre for Genome Research and Medical Systems Biology, Berlin, Germany.|Alacris Theranostics GmbH, Berlin, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.|University of Zurich, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Moelling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009368:Neoplasm Transplantation; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D059467:Transcriptome; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: PDZ domain; c-Src; metastasis; oncogene; transcriptome