Related Experiment Video
Updated: Jan 16, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy
Nina Wang1,2,3, Qian Sun1,2,3, Daniel Novak1,2,3
1Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract:
Targeted therapy has been established as a therapeutic option for the treatment of metastatic melanoma. Despite initially being very efficient, many tumors develop resistance to targeted therapy, leading to its failure. We previously demonstrated that the neural crest (NC)-associated gene ERRFI1 is highly expressed in metastatic melanoma and correlates with a bad prognosis. Here, we show that the expression of ERRFI1 was upregulated in melanoma and negatively correlated with the expression of melanocytic differentiation markers, such as MITF and TYR. Downregulation of ERRFI1 with the help of siRNA increased the susceptibility of melanoma cells toward BRAF inhibition (BRAFi) and resensitized BRAFi-resistant melanoma cells to BRAFi. Mass spectrometry-based proteomic analysis revealed that ERRFI1 silencing diminished the activation of the mitogen-activated protein kinase (MAPK) and AKT signaling pathways, which usually contribute to drug resistance. Furthermore, we show that miR-200c targeted the 3'UTR of ERRFI1 and reduced its expression, resulting in the resensitization of BRAFi-resistant melanoma cells to BRAFi. Our study results suggest that ERRFI1 could be a potential therapeutic target for the treatment of metastatic melanoma.
Insights
Targeted therapy resistance in melanoma can be overcome by targeting the ERRFI1 gene. Reducing ERRFI1 expression resensitizes melanoma cells to BRAF inhibition therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted therapy is a key treatment for metastatic melanoma but often fails due to drug resistance.
- The neural crest-associated gene ERRFI1 is highly expressed in metastatic melanoma and linked to poor prognosis.
Purpose of the Study:
- To investigate the role of ERRFI1 in melanoma drug resistance.
- To explore ERRFI1 as a potential therapeutic target for overcoming resistance to BRAF inhibition (BRAFi).
Main Methods:
- Analyzing ERRFI1 expression in melanoma.
- Using siRNA to downregulate ERRFI1 expression.
- Employing mass spectrometry-based proteomic analysis.
- Investigating the role of miR-200c in ERRFI1 regulation.
Main Results:
- ERRFI1 expression is upregulated in melanoma and inversely correlated with differentiation markers (MITF, TYR).
- ERRFI1 downregulation increased melanoma cell sensitivity to BRAFi and resensitized resistant cells.
- Silencing ERRFI1 reduced MAPK and AKT signaling pathway activation.
- miR-200c targets ERRFI1, reducing its expression and resensitizing resistant melanoma cells to BRAFi.
Conclusions:
- ERRFI1 plays a significant role in melanoma drug resistance.
- Targeting ERRFI1, potentially via miR-200c, offers a strategy to resensitize melanoma to BRAFi.
- ERRFI1 represents a promising therapeutic target for metastatic melanoma treatment.
Related Concept Videos
02:38Mitogens and the Cell Cycle
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
01:51Determination