SMAD4 and chordoma: IHC analysis of the metastatic sacral chordoma model CF466 showed increased nuclear retention of the XPO1 cargo SMAD4, which is an upstream regulator of Brachyury (47), and slightly reduced expression of both Brachyury and its downstream target YAP1, a hippo signaling pathway member that can control tumor stemness and aggressiveness (48).