A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer.

We previously analyzed expression profiles of 20 colorectal tumors by means of genome-wide cDNA microarray. Among the genes that were commonly up-regulated in the CRCs, we further characterized biological importance of a novel human gene termed RNF43 (RING finger protein 43) in colorectal carcinogenesis. Multiple-tissue northern blot analysis revealed undetectable expression of RNF43 in normal adult tissues examined and low levels of expression in fetal kidney and lung. Its exogenous expression conferred a growth-promoting effect in COS7 and NIH3T3 cells, and suppression of its expression by specific short interfering RNAs retarded the growth of colon cancer cells. Interestingly, RNF43 protein was shown to be a secreted protein, and addition of the conditioned media of the RNF43-transfected cells into culture media of NIH3T3 cells revealed a significant enhancement of cell growth. These data suggest that RNF43 may exert its growth promoting effect in an antocrine manner, and that it may be a novel diagnostic marker for colorectal cancer.