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Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 5, p e0177830 (2017)
- Publication Year :
- 2017
-
Abstract
- ILEI (FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. Initially, we found that ILEI mRNA is highly expressed in melanoma metastases but not in primary tumors, suggesting that ILEI contributes to the malignant properties of melanoma. While melanoma is not an epithelial cell-derived tumor and does not undergo a traditional EMT, melanoma undergoes a similar process known as phenotype switching in which high (micropthalmia-related transcription factor) MITF expressing (MITF-high) proliferative cells switch to a low expressing (MITF-low) invasive state. We observed that MITF-high proliferative cells express low levels of ILEI (ILEI-low) and MITF-low invasive cells express high levels of ILEI (ILEI-high). We found that inducing phenotype switching towards the MITF-low invasive state increases ILEI mRNA expression, whereas phenotype switching towards the MITF-high proliferative state decreases ILEI mRNA expression. Next, we used in vitro assays to show that knockdown of ILEI attenuates invasive potential but not MITF expression or chemoresistance. Finally, we used gene expression analysis to show that ILEI regulates several genes involved in the MITF-low invasive phenotype including JARID1B, HIF-2α, and BDNF. Gene set enrichment analysis suggested that ILEI-regulated genes are enriched for JUN signaling, a known regulator of the MITF-low invasive phenotype. In conclusion, we demonstrate that phenotype switching regulates ILEI expression, and that ILEI regulates partial phenotype switching in MITF-low melanoma cell lines.
- Subjects :
- 0301 basic medicine
Melanomas
Cell
lcsh:Medicine
Gene Expression
Biochemistry
Cell Movement
Medicine and Health Sciences
Enzyme assays
Gene Regulatory Networks
Colorimetric assays
Neoplasm Metastasis
lcsh:Science
Melanoma
Bioassays and physiological analysis
Regulation of gene expression
Cultured Tumor Cells
Gene knockdown
Multidisciplinary
MTT assay
integumentary system
Messenger RNA
Microphthalmia-associated transcription factor
Phenotype
Neoplasm Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
Nucleic acids
Phenotypes
Immunoblot Analysis
medicine.anatomical_structure
Oncology
Cytokines
Melanoma Cells
Biological Cultures
Research Article
Epithelial-Mesenchymal Transition
Molecular Probe Techniques
Biology
Research and Analysis Methods
03 medical and health sciences
Cell Line, Tumor
medicine
Genetics
Humans
Gene Regulation
Epithelial–mesenchymal transition
Molecular Biology Techniques
Molecular Biology
Cell Proliferation
Microphthalmia-Associated Transcription Factor
Cell growth
lcsh:R
Biology and Life Sciences
Cancers and Neoplasms
Cell Cultures
medicine.disease
body regions
030104 developmental biology
Biochemical analysis
Cancer research
RNA
lcsh:Q
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....76e503b628b04b065c7b541bdfd64aeb