SEL1L exerts a pro-tumorigenic/pro-angiogenic function in human skin melanoma

Area of Science:

• Molecular Biology
• Oncology
• Cell Biology

Background:

• Suppressor/enhancer of Lin-12-like (SEL1L) is involved in the endoplasmic reticulum-associated degradation (ERAD) and unfolded protein response (UPR) pathways.
• The role of SEL1L in human cutaneous malignant melanoma (cMM) is largely unexplored, with potential pro-tumorigenic or oncosuppressive functions in other cancers.

Purpose of the Study:

• To investigate the role and potential function of SEL1L in human cutaneous malignant melanoma (cMM).
• To determine SEL1L expression levels in cMM and their correlation with clinical parameters and patient survival.

Main Methods:

• In silico analysis of SEL1L expression in cMM.
• Immunohistochemistry and quantitative digital morphometric analysis of SEL1L protein in tumor samples.
• In vivo studies involving SEL1L-silenced melanoma cells grafted in immunodeficient mice.
• In vitro and in vivo assays to assess angiogenic potential.

Main Results:

• SEL1L is upregulated in cMM and correlates with higher Clark level, poorer survival, increased tumor thickness, and ulceration.
• SEL1L expression is linked to ER-stress responses and correlates with microvessel density in cMM.
• Silencing SEL1L in melanoma cells reduced tumor proliferation, enhanced apoptosis, increased necrosis, and decreased vascularization.

Conclusions:

• SEL1L exhibits a pro-tumorigenic and pro-angiogenic function in human melanoma.
• SEL1L represents a potential therapeutic target for cutaneous malignant melanoma.