PIK3CA and breast cancer: mTORC1 has been shown to exert its various functions in cancer through activation by upstream molecules including, but not limited to, TGFβ, MAPK, Src, phospholipase D, and PI3K (the best characterized activator of mTORC1).31–34,42,50–52 Our efforts to find the main kinase connecting RON and mTORC1 in human breast cancer revealed PI3K, rather than MAPK, as the dominant upstream kinase.