ERBB2 and neoplasm: It has been demonstrated that TGF-β cooperated with HER2 at various levels, including transcriptional regulation of the Smad target genes and pathways; activation of the PI3K/Akt pathway in a Smad-independent manner; modification of the tumor microenvironment by inducing the secretion of TGF-β, Erb2 ligands, and angiogenic mediators [18].