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Updated: Jun 8, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
DTL promotes the growth and migration of melanoma cells through the ERK/E2F1/BUB1 axis
Xiuyun Xuan1, Juanmei Cao1,2, Li Chen3
1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
Abstract:
Melanoma is the most dangerous form of skin cancer. Hence, a better understanding of molecular mechanisms in melanoma pathogenesis is urgently needed, which provides a new insight into the therapy of melanoma. DTL gene is screened out in melanoma pathogenesis by integrated bioinformatics analysis, and its expression is validated in the tissue and cell samples of melanoma. Forced DTL expression facilitates the proliferation, invasion, migration and EMT of melanoma cells, while DTL knockdown suppresses the biological behavior of melanoma cells. In addition, DTL promotes the malignancy of melanoma in vivo. Mechanistically, BUB1 is the crucial downstream target of DTL. Reduced DTL expression suppresses BUB1 expression, while enhanced DTL expression induces BUB1 upregulation. Rescue experiments showed that growing and migrating of melanoma cells induced by DTL are partially impaired by BUB1 inhibition. In addition, the expression of phosphorylated ERK (p-ERK) and the downstream transcription factor E2F1 are reduced when DTL expression is blocked. Meanwhile, BUB1 levels are decreased when the expression of p-ERK or E2F1 is repressed. Notably, the growth and migration of melanoma cells by inhibition of ERK and knockdown of E2F1 was rescued by overexpressing BUB1. DTL gene may be a prognosis marker and represent a unique potential target for melanoma patients. DTL supports the biologically malignant activity of melanoma cells via the ERK/E2F1/BUB1 axis.
Insights
The DTL gene drives melanoma progression by promoting cell proliferation, invasion, and migration through the ERK/E2F1/BUB1 pathway. Targeting DTL offers a potential therapeutic strategy for melanoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Melanoma is a dangerous skin cancer requiring better understanding of its pathogenesis.
- Identifying novel molecular targets is crucial for advancing melanoma therapy.
Purpose of the Study:
- To investigate the role of the DTL gene in melanoma pathogenesis.
- To elucidate the molecular mechanisms underlying DTL's function in melanoma.
Main Methods:
- Integrated bioinformatics analysis to screen for relevant genes.
- Validation of DTL expression in melanoma tissues and cells.
- In vitro experiments assessing cell behavior (proliferation, invasion, migration, EMT) with DTL manipulation.
- In vivo studies to evaluate DTL's effect on melanoma malignancy.
- Mechanistic studies involving downstream targets (BUB1, ERK, E2F1) and rescue experiments.
Main Results:
- DTL gene expression is upregulated in melanoma and associated with increased proliferation, invasion, migration, and EMT.
- DTL knockdown suppresses melanoma cell malignancy both in vitro and in vivo.
- BUB1 is a key downstream target of DTL, mediating its effects on cell growth and migration.
- DTL regulates the ERK/E2F1/BUB1 signaling axis, which is critical for melanoma cell behavior.
Conclusions:
- DTL promotes melanoma malignancy via the ERK/E2F1/BUB1 pathway.
- DTL represents a potential prognostic marker and therapeutic target for melanoma.
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