NDLI: RNA-seq analysis reveals significant effects of EGFR signalling on the secretome of mesenchymal stem cells

Content Provider	PubMed Central
Author	Luca, Antonella De Roma, Cristin Gallo, Marianna Francesca, Fenizia Francesca, Bergantino Frezzetti, Daniela Costantini, Susan Nicola, Normanno
Copyright Year	2014
Abstract	Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNA-sequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα. We identified 1,640 highly differentially regulated genes: 967 genes up-regulated with Fold Induction (FI)≥1.50 and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or surface receptors resulted enriched following TGFα treatment, including VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3. Secretion of corresponding proteins was confirmed for selected factors. Finally, we identified 4,377 and 4,262 alternatively spliced genes in untreated and TGFα-treated MSCs, respectively. Among these, an unannotated splice variant of VEGFA coding for a secreted VEGF protein of 172 aminoacids (VEGFA172), was found only in MSCs stimulated with TGFα. These findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression.
Ending Page	10528
Starting Page	10518
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	21
Volume Number	5
Language	English
Publisher	Impact Journals LLC
Publisher Date	2014-10-29
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

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