Universität zu Köln

Broecker, Felix, Hardt, Christopher, Herwig, Ralf ORCID: 0000-0002-9335-1760, Timmermann, Bernd, Kerick, Martin ORCID: 0000-0002-6298-4514, Wunderlich, Andrea, Schweiger, Michal R., Borsig, Lubor ORCID: 0000-0003-2263-9545, Heikenwalder, Mathias, Lehrach, Hans and Moelling, Karin (2016). Transcriptional signature induced by a metastasis-promoting c-Src mutant in a human breast cell line. FEBS J., 283 (9). S. 1669 - 1689. HOBOKEN: WILEY. ISSN 1742-4658

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Broecker, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Hardt, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Herwig, Ralf UNSPECIFIED orcid.org/0000-0002-9335-1760 UNSPECIFIED Timmermann, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerick, Martin UNSPECIFIED orcid.org/0000-0002-6298-4514 UNSPECIFIED Wunderlich, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borsig, Lubor UNSPECIFIED orcid.org/0000-0003-2263-9545 UNSPECIFIED Heikenwalder, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehrach, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Moelling, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-276628
DOI:	10.1111/febs.13694
Journal or Publication Title:	FEBS J.
Volume:	283
Number:	9
Page Range:	S. 1669 - 1689
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1742-4658
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-BINDING PROPERTIES; FOCAL ADHESION KINASE; V-SRC; TRANSFORMATION FINGERPRINT; TYROSINE PHOSPHATASE; MESSENGER-RNA; CANCER; PROTEIN; EXPRESSION; INVASION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27662