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


RESULTS
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.


CONCLUSIONS
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.
Stewart
Grant D
GD
Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary, Edinburgh, UK. grant.stewart@ed.ac.uk
Skipworth
Richard Je
RJ
Ross
James A
JA
Fearon
Kenneth Ch
KCh
Baracos
Vickie E
VE
D000818:Animals; D002100:Cachexia / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D010455:Peptides; D011509:Proteoglycans; C442243:dermcidin; C042057:proteolysis-inducing peptide