SMAD4 and neoplasm: However, in later stages of cancer, SMAD4’s genetic/epigenetic alterations impair TGF-β’s tumor-suppressive function [25], wherein the expression of transcription factors such as snail family transcriptional repressor 1 (SNAIL), snail family transcriptional repressor 2 (SLUG), zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) is enhanced leading to upregulation of mesenchymal markers (N-cadherin, vimentin, fibronectin) and downregulation of epithelial markers (E-cadherin, Claudin-1) [26].