Transcriptome profiling reveals novel gene expression signatures and regulating transcription factors of TGFβ-induced epithelial-to-mesenchymal transition.
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 MCF10a. 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, IRF5 and LMCD1, were identified and independently validated.
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.
Liutao
L
Du
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.
Shota
S
Yamamoto
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.
Barry L
BL
Burnette
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.
Danshang
D
Huang
Department of Neurology, UCLA, Los Angeles, California, 90095.
Kun
K
Gao
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.
Neema
N
Jamshidi
Department of Radiology, The David Geffen School of Medicine at UCLA, Los Angeles, California, 90095.|Department of Bioengineering, University of California-Los Angeles, Los Angeles, California, 90095.
Michael D
MD
Kuo
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015203:Reproducibility of Results; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D056970:Co-Repressor Proteins; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D060588:LIM Domain Proteins; C406239:LMCD1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
Breast; epithelial to mesenchymal transition; genomics, transcription factor; non-small-cell lung cancer