Although the loss of SMAD4 inhibits the canonical TGF-β signaling, it has also been shown to induce BMP signaling to switch from tumor suppression to increased EMT, invasion, and metastasis promotion, which occur via the activation of Rho signaling through Rho-associated protein kinase (ROCK) and LIM domain kinase (LIMK) [85]. Here, SMAD4 is linked to neoplasm.