The regulation of melanogenesis has been investigated as a long-held aim for pharmaceutical manipulations with denotations for malignancy of melanoma. Mucins have protective function in epithelial organs however, the most outer organ, skin, the role of mucins has not studied enough.

Our initial hypothesis developed from the identification of correlations between pigmentation and expressions of skin mucins, particularly those exists in skin tissue. We try to investigate the action of mucins in human melanocytic cells.

The expression of mucin proteins in human skin was investigated using microarray data from Human Protein Atlas consortium and genome-based tissue expression consortium database. Mucin expression was measured at RNA and protein level in melanoma cells. Findings were further validated and confirmed by analysis of independent experiments.

We found out that the several mucin proteins showed expressions in human skin cells and among these, mucin-like protein 1 (MUCL1) showed highest expression and also clear negative correlation with melanogenesis in epidermal melanocytes. We confirmed the correlations between melanogenesis and MUCL1 by revealing negative correlations in melanocytes with different melanin production, resulting from increased composition of threonine, mucin-conforming amino acid, and increased autophagy-related forkhead-box O signaling. Furthermore, threonine itself affects melanogenesis and metastatic activity in melanoma cells.

We identified a significant association between MUCL1/Threonine with melanogenesis and metastasis-related genes in melanoma cells. Our results define a novel mechanism of mucin regulation, suggesting a diagnostic role and preventive actions of MUCL1 in cutaneous melanoma.