SOX2 contributes to melanoma cell invasion.

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Melanoma invasion mechanisms remain unclear.
• SRY (sex determining region Y)-box 2 (SOX2), an embryonic stem cell factor, is found in human melanoma and linked to invasion and tumor thickness.

Purpose of the Study:

• To investigate the role of SOX2 expression in melanoma invasion.
• To identify potential mediators of SOX2-driven melanoma invasion.

Main Methods:

• Examined SOX2 expression in patient melanomas and xenografts.
• Performed experimental knockdown (KD) and overexpression of SOX2 in melanoma cell lines.
• Analyzed expression of invasion-related genes using RT-PCR.
• Assessed the impact of SOX2 and matrix metalloproteinase-3 (MMP-3) KD on melanoma invasiveness.

Main Results:

• SOX2 was preferentially expressed in cells infiltrating the dermal stroma.
• SOX2 KD decreased melanoma cell invasiveness by 4.5-fold; SOX2 overexpression increased invasiveness by 3.8-fold.
• SOX2 KD significantly reduced matrix metalloproteinase-3 (MMP-3) mRNA levels by 87.8%.
• MMP-3 KD partially inhibited invasion in SOX2-expressing cells.
• Coordinate SOX2 and MMP-3 expression was observed in stromal-infiltrating melanoma cells.

Conclusions:

• SOX2 expression is implicated in driving melanoma invasion.
• MMP-3 is suggested as a potential mediator of SOX2-induced melanoma invasion.