TGFB1 and neoplasm: In addition, the HMGA2 protein also stimulates the TGF-β, MAPK, and PI3K signaling pathways, which in turn increases HMGA2 expression within a positive feedback loop, causing a significant increase in HMGA2 levels as the tumor reaches the stage of muscle invasion (Tan et al. 2016; Voon et al. 2013; Ayoubi et al. 1999).