Related Experiment Video

Updated: Mar 1, 2026

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Published on: November 11, 2016

Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines

Ken Noguchi¹, Annamarie C Dalton¹, Breege V Howley¹

¹Department of Biochemistry and Molecular Biology, College of Medicine, Medical University of South Carolina, Charleston, SC, United States of America.

|May 26, 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.

Insights

Interleukin-like element I (ILEI) promotes melanoma cell invasion by regulating phenotype switching. ILEI expression increases as melanoma cells transition to an invasive state, driving metastatic potential.

Area of Science:

Oncology
Cell Biology
Molecular Biology

Background:

The epithelial-to-mesenchymal transition (EMT) confers metastatic properties to tumor cells.
Melanoma exhibits a similar process called phenotype switching, involving a shift from high MITF (micropthalmia-related transcription factor) to low MITF expression.
Interleukin-like element I (ILEI, FAM3C) is a secreted factor implicated in EMT.

Purpose of the Study:

To investigate the role of ILEI in melanoma phenotype switching and its contribution to metastatic properties.
To determine the relationship between MITF expression levels and ILEI expression in melanoma cells.
To identify downstream targets and signaling pathways regulated by ILEI in invasive melanoma.

Main Methods:

Analysis of ILEI mRNA expression in melanoma metastases versus primary tumors.
Induction of phenotype switching in melanoma cells and assessment of ILEI expression changes.
In vitro assays to evaluate the effect of ILEI knockdown on melanoma cell invasion.
Gene expression analysis and gene set enrichment analysis to identify ILEI-regulated genes and pathways.

Main Results:

ILEI mRNA is highly expressed in melanoma metastases but not primary tumors.
Melanoma cells with low MITF (invasive) express high ILEI, while high MITF (proliferative) cells express low ILEI.
Inducing an invasive phenotype increases ILEI expression; inducing a proliferative phenotype decreases ILEI expression.
ILEI knockdown attenuates melanoma cell invasion but does not affect MITF expression or chemoresistance.
ILEI regulates genes associated with the invasive phenotype, including JARID1B, HIF-2α, and BDNF.
ILEI-regulated genes are enriched for JUN signaling, a known regulator of melanoma invasion.

Conclusions:

Phenotype switching in melanoma is a key regulator of ILEI expression.
ILEI plays a significant role in promoting the invasive phenotype of melanoma cells.
ILEI contributes to partial phenotype switching in MITF-low melanoma cell lines, highlighting its role in melanoma progression and metastasis.

Read full analysis

More Related Videos

Direct Reprogramming of Mouse Fibroblasts into Melanocytes

Direct Reprogramming of Mouse Fibroblasts into Melanocytes

Published on: August 27, 2021

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

Related Concept Videos

Forced Transdifferentiation

Forced Transdifferentiation

Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

Articles linked to this work by shared authors, journal, and citation graph.

Association Between Appetite and Physical Activity in Community-Dwelling Older Adults: Focusing on Activity Intensity and Duration.

Journal of aging and physical activity·2026

Rotor-guided tailor-made pulmonary vein isolation for persistent atrial fibrillation: Identification of the left atrial septum as a common arrhythmogenic substrate.

Heart rhythm O2·2026

Curative treatment is feasible for recurrent hepatocellular carcinoma regardless of recurrence pattern after hepatitis C virus eradication with interferon-free direct-acting antiviral therapy.

BMC gastroenterology·2026

Three-Week Monitoring After Anamorelin Initiation in Unresectable or Recurrent Pancreatic Cancer: Dietary Intake Category, Observed Body Weight, and Prognostic Nutritional Index.

Journal of palliative medicine·2026

Exfoliating effect of β-glycyrrhetinic acid on plaque inducing gingivitis: Comparison with cetylpyridinium chloride.

PloS one·2026

A Step-Up Underwater Endoscopic Mucosal Resection Strategy with Rescue Underwater Injection Endoscopic Mucosal Resection for Non-Pedunculated Colorectal Lesions.

DEN open·2026

See all related articles