Revisiting olfactory receptors as putative drivers of cancer

Background: Olfactory receptors (ORs) recognize odorant molecules and activate a signal transduction pathway that ultimately leads to the perception of smell. This process also modulates the apoptotic cycle of olfactory sensory neurons in an olfactory receptor-specific manner. Recent reports indicate that some olfactory receptors are expressed in tissues other than the olfactory epithelium suggesting that they may have pleiotropic roles. Methods: We investigated the expression of 301 olfactory receptor genes in a comprehensive panel of 968 cancer cell lines. Results: Forty-nine per cent of cell lines show expression of at least one olfactory receptor gene. Some receptors display a broad pattern of expression across tumour types, while others were expressed in cell lines from a particular tissue. Additionally, most of the cancer cell lines expressing olfactory receptors express the effectors necessary for OR-mediated signal transduction. Remarkably, among cancer cell lines, OR2C3 is exclusively expressed in melanoma lines. We also confirmed the expression of OR2C3 in human melanomas, but not in normal melanocytes. Conclusions: The pattern of OR2C3 expression is suggestive of a functional role in the development and/or progression of melanoma. Some olfactory receptors may contribute to tumorigenesis.