Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell linesReport as inadecuate




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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.



Author: Ken Noguchi, Annamarie C. Dalton, Breege V. Howley, Buckley J. McCall, Akihiro Yoshida, J. Alan Diehl, Philip H. Howe

Source: http://plos.srce.hr/



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