“…TGF‐β/ALK5/Smad signaling plays opposite roles in cancer progression (Connolly et al, 2011; Gu & Feng, 2018; M. Zhang et al, 2011). Acting as a tumor suppressor, TGF‐β/ALK5/Smad signaling inhibits proliferation and enhances differentiation by activating cyclin‐dependent kinase inhibitors, such as p16INK4a, p21cip1, and p27Kip1, and downregulating transcription factors, such as Myc, Id1, and Id2, in normal epithelial cells and premalignant lesion cells (S. H. Choi, Barker, Gerber, Letterio, & Kim, 2020; Sadek, Mahmoud, Zeweil, & Abouzed, 2021; Visram, Dasari, Anderson, Kumar, & Kourelis, 2021). In contrast, when malignant tumor reaches an advanced stage, TGF‐β/ALK5/Smad promotes tumor progression prominently by inducing EMT, reinforcing tumor–stroma interaction, and leading to escaping immune system surveillance.…”