Envoplakin Inhibits Macrophage Polarization by Altering the Inflammatory Tumor Microenvironment of Melanoma Through...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Melanoma is a highly metastatic cancer, necessitating novel therapeutic targets to inhibit tumor progression and modulate the tumor microenvironment.
• Tumor growth creates a transitional zone at the margin, rich in immune cells, highlighting the immune system's role in melanoma.
• Epidermal proliferation factor-like (EVPL) is identified as a potential prognostic biomarker for melanoma, warranting further investigation into its role.

Purpose of the Study:

• To investigate the role of EVPL in melanoma progression and its impact on the tumor microenvironment.
• To explore the association of EVPL with key signaling pathways, such as the Ras/Raf pathway, in melanoma.
• To evaluate EVPL as a potential therapeutic target for inhibiting melanoma metastasis and regulating immune cell infiltration.

Main Methods:

• Differential gene expression analysis was performed on normal skin, nevus, and melanoma samples to identify key genes.
• Bioinformatic approaches were used to identify hub genes and enriched pathways related to melanoma's inflammatory response.
• In vitro assays (CCK-8, colony formation, wound healing, Transwell, flow cytometry) assessed melanoma cell proliferation, migration, invasion, and apoptosis. Macrophage recruitment and polarization were studied using co-culture systems and Western blot analysis.

Main Results:

• EVPL was identified as a hub gene associated with the Ras/Raf pathway and involved in regulating melanoma's inflammatory microenvironment.
• Overexpression of EVPL (Oe-EVPL) suppressed melanoma cell malignant progression.
• EVPL inhibited chemokine expression, macrophage recruitment, and polarization via the Ras/Raf/ERK signaling pathway, reversing inhibitory effects induced by pathway inhibitors.

Conclusions:

• EVPL inhibits melanoma progression by modulating the RAS/ERK signaling pathway.
• EVPL plays a crucial role in altering the inflammatory tumor microenvironment of melanoma.
• EVPL effectively inhibits macrophage recruitment, suggesting its therapeutic potential in melanoma treatment.