PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Broecker, F.* ; Hardt, C.* ; Herwig, R.* ; Timmermann, B.* ; Kerick, M.* ; Wunderlich, A.* ; Schweiger, M.R.* ; Borsig, L.* ; Heikenwälder, M. ; Lehrach, H.* ; Moelling, K.*

Transcriptional signature induced by a C-terminal c-Src mutant in a human breast cell line.

FEBS J. 283, 1669-1688 (2016)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are characteristic of the viral oncogene protein v-Src and are present in some advanced human colon cancers. They are associated with increased kinase activity and elevated cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison to its wildtype protein, c-Src(wt), expressed in the human non-transformed breast epithelial cell line MCF-10A. We demonstrated previously that the mutant changed migratory and metastatic properties. Genome-wide transcriptome analysis revealed that c-Src(mt) deregulated the expression levels of about 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. More than 80% of these genes have previously been linked to cellular migration, while the others play roles, for instance, in RNA transport and splicing processes. Consistent with the transcriptome data, c-Src(mt)-, but not c-Src(wt)-expressing cells showed the capacity to metastasize into mouse lung tissue in vivo. The mRNA expression profile of c-Src(mt)-expressing cells shows significant overlap with that of various primary human tumor samples, perhaps reflecting elevated Src activity in some cancerous cells. Expression of c-Src(mt) lead to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. We identified genes and pathways deregulated by c-Src(mt) as biomarkers with potential interest for diagnostics or therapy of metastatic cells.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.237
1.111
5
8
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Oncogene ; Pdz Domain ; C-src ; Metastasis ; Migration ; Transcriptome; Focal Adhesion Kinase; Protein-tyrosine-phosphatase; Dna-binding Properties; V-src; Messenger-rna; Cancer Cells; Transformation Fingerprint; Prostate-cancer; Target Genes; Human Genome
Language
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1742-464X
e-ISSN 1742-4658
Journal FEBS Journal, The
Quellenangaben Volume: 283, Issue: 9, Pages: 1669-1688 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-551600-001
DOI 10.1111/febs.13694
WOS ID WOS:000376601900007
Scopus ID 84961653982
PubMed ID 26919036
Erfassungsdatum 2016-03-03
[➜Report correction]