The dermcidin gene in cancer: role in cachexia, carcinogenesis and tumour cell survival

• Published in: Current opinion in clinical nutrition and metabolic care Vol. 11; no. 3; p. 208
• Main Authors: Stewart, Grant D, Skipworth, Richard Je, Ross, James A, Fearon, Kenneth Ch, Baracos, Vickie E
• Format: Journal Article
• Language: English
• Published: England 01.05.2008
• Subjects: Animals; Cachexia - genetics; Cachexia - metabolism; Cell Survival; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Neoplasms - genetics; Peptides - genetics; Peptides - metabolism; Peptides - physiology; Proteoglycans - genetics; Proteoglycans - metabolism; Proteoglycans - physiology; Tumor Cells, Cultured
• ISSN: 1363-1950
• DOI: 10.1097/MCO.0b013e3282fb7b8d

The diverse protein products of the dermcidin gene are relevant to immunity, cancer cell progression and cancer cachexia. This article evaluates recent developments/controversies around dermcidin. Dermcidin has recently been shown to act as a survival/proliferation factor in hepatoma and prostate cancer cell lines. Recent studies suggest that the Y-P30 subunit of the dermcidin polypeptide offers a survival advantage in such cancer cells. Nevertheless, the relevance of Y-P30 to cancer growth in vivo, and mechanisms of action remain unknown. In mice, tumour cells appear to glycosylate the Y-P30 subunit, transforming it into a potent skeletal muscle proteolysis-inducing factor. Recent work has described a receptor and signal transduction pathways for murine glycosylated proteolysis-inducing factor. The absence of classical N-glycosylation sites in the human proteolysis-inducing factor peptide and the lack of specific tools for the detection of the key carbohydrate moieties conferring the proteolysis-inducing activity, however, remain barriers to confirming glycosylated proteolysis-inducing factor as a pro-cachectic factor in humans. There is a growing body of evidence illustrating dermcidin as an oncogene and Y-P30 as a survival factor. The biology of murine proteolysis-inducing factor as a pro-cachectic factor continues to evolve; however, its role in human biology remains speculative.