Figure 4.

Cell signaling from the RTK c-Kit is disrupted during tumor development in a subset of salivary gland ACCs. C-Kit regulates cell survival and growth control through the PI3K/Akt and MAPK signaling pathways. We found inactivating mutations in KIT, KRAS, and BRAF. Because ACC can proliferate despite inactivation of c-Kit cell signaling, c-Kit must be dispensable for maintaining established ACC tumors. This is the first time that inactivation of MAPK accompanied tumorigenesis. Our results also suggest that selective inhibition of c-Kit is not a promising strategy for ACC therapeutic development.