ERBB2 and neoplasm: Our recent studies demonstrate that TGF-β and HER2 cooperate at various levels, including (1) transcriptional regulation of the Smad target genes and pathways; (2) activation of the PI3K/Akt pathway in a Smad-independent manner; (3) modification of the tumor microenvironment by inducing the secretion of TGF-β, ErbB ligands, and angiogenic mediators.