In this sense, the antagonism of the TMED9-TGFα and TMED3-WNT loops may not act solely cell autonomously, with the final balance and outcome being influenced by both signaling within tumor cells and from the surrounding stroma: the cancer cell-intrinsic and the stroma-to-cancer cell pro-metastatic functions of TGFα may therefore coexist and cooperate ([89, 90]; this work). This evidence concerns the gene TMED3 and neoplasm.