Title : FAM46C: a new tumour suppressor with a broad anticancer potential
Abstract:
FAM46C is an oncosuppressor gene which is found mutated in approximately 10% of multiple myeloma (MM) patients. Recently, we proposed a model to explain FAM46C mode of action in MM. In highly-secreting MM cells, FAM46C regulates intracellular trafficking and protein secretion dynamics, causing inhibition of autophagy and consequent accumulation of intracellular protein aggregates, an event which in turn triggers apoptosis. This effect is completely abolished by the most frequently found mutant variants of FAM46C, indicating that this activity is responsible for FAM46C oncosuppressor function. Besides describing FAM46C mode of action we also found that the expression of the wt form of FAM46C, but of none of its mutant variants, sensitizes MM cells to sphingosine kinase (SK) inhibition. Since SKs are proteins involved in ceramide metabolism, a pathway that is frequently altered in cancer cells, and SK inhibitors are currently being proposed as anti-cancer drugs, these findings underline the potential therapeutic importance of determining FAM46C mutational status in patients in order to define personalized treatment options. Emerging evidence is underlining the involvement of FAM46C in different cancer types, hence, our findings are of broad interest for the cancer research community as they might be relevant for implementing global anti-cancer strategies.
