Open AccessTranscriptome profiling reveals novel gene expression signatures and regulating transcription factors of TGF β ‐induced epithelial‐to‐mesenchymal transition
Author(s) -
Du Liutao,
Yamamoto Shota,
Burnette Barry L.,
Huang Danshang,
Gao Kun,
Jamshidi Neema,
Kuo Michael D.
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.719
Subject(s) - epithelial–mesenchymal transition , transcriptome , biology , cancer research , gene expression profiling , transforming growth factor beta , transcription factor , gene signature , mesenchymal stem cell , microarray analysis techniques , gene expression , transforming growth factor , cancer , microbiology and biotechnology , gene , metastasis , genetics
Dysregulated epithelial to mesenchymal transition ( EMT ) in cancer cells endows invasive and metastatic properties upon cancer cells that favor successful colonization of distal target organs and therefore play a critical role in transforming early‐stage carcinomas into invasive malignancies. EMT has also been associated with tumor recurrence and drug resistance and cancer stem cell initiation. Therefore, better understanding of the mechanisms behind EMT could ultimately contribute to the development of novel prognostic approaches and individualized therapies that specifically target EMT processes. As an effort to characterize the central transcriptome changes during EMT , we have developed a Transforming growth factor ( TGF )‐beta‐based in vitro EMT model and used it to profile EMT ‐related gene transcriptional changes in two different cell lines, a non‐small cell lung cancer cell line H358, and a breast cell line MCF 10a. After 7 days of TGF ‐beta/Oncostatin M ( OSM ) treatment, changes in cell morphology to a mesenchymal phenotype were observed as well as concordant EMT ‐associated changes in mRNA and protein expression. Further, increased motility was noted and flow cytometry confirmed enrichment in cancer stem cell‐like populations. Microarray‐based differential expression analysis identified an EMT ‐associated gene expression signature which was confirmed by RT ‐ qPCR and which significantly overlapped with a previously published EMT core signature. Finally, two novel EMT ‐regulating transcription factors, IRF 5 and LMCD 1, were identified and independently validated.