Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Autor: Bidyut K. Mohanty, Breege V. Howley, Buckley J. McCall, Toros Dincman, Annamarie C. Dalton, Ken Noguchi, Philip H. Howe
Rok vydání: 2018
Předmět:
Transcriptional Activation
0301 basic medicine
Epithelial-Mesenchymal Transition
mRNA
Cell
phenotype switching
Biochemistry
Upstream Stimulatory Factor
Cell Line
Mice
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
melanoma
cytokine
medicine
Transcriptional regulation
Animals
Humans
Gene Regulation
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Molecular Biology
Transcription factor
transcription factor
FAM3C
Cells
Cultured
USF-1
Gene knockdown
ILEI
Chemistry
Melanoma
Cell Biology
medicine.disease
Neoplasm Proteins
Up-Regulation
3. Good health
Gene Expression Regulation
Neoplastic
epithelial-mesenchymal transition (EMT)
030104 developmental biology
medicine.anatomical_structure
interleukin-like EMT inducer
Cancer research
Cytokines
Upstream Stimulatory Factors
Zdroj: The Journal of Biological Chemistry
ISSN: 0021-9258
DOI: 10.1074/jbc.ra118.003616
Popis: Interleukin-like EMT inducer (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. However, very little is known about how ILEI is regulated. Here we demonstrate that ILEI is an in vivo regulator of melanoma invasiveness and is transcriptionally up-regulated by the upstream stimulatory factor-1 (USF-1), an E-box–binding, basic-helix-loop-helix family transcription factor. shRNA-mediated knockdown of ILEI in melanoma cell lines attenuated lung colonization but not primary tumor formation. We also identified the mechanism underlying ILEI transcriptional regulation, which was through a direct interaction of USF-1 with the ILEI promoter. Of note, stimulation of endogenous USF-1 by UV-mediated activation increased ILEI expression, whereas shRNA-mediated USF-1 knockdown decreased ILEI gene transcription. Finally, we report that knocking down USF-1 decreases tumor cell migration. In summary, our work reveals that ILEI contributes to melanoma cell invasiveness in vivo without affecting primary tumor growth and is transcriptionally up-regulated by USF-1.
Databáze: OpenAIRE
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