Colon cancer is one of the most common cancers in the developed countries. The association between transforming growth factor TGF alpha and human cancer incidence has been suggested, yet, the regulatory roles of TGF alpha and the molecular mechanisms remain unknown, especially in colon cancer. We aim to investigate the functional regulations of TGF alpha in colon cancer progression. Two colon cancer cell lines were applied, and plasmid overexpression and siRNA-mediated depletion techniques were used to verify the role of TGF alpha in colon cancer. Cell proliferation was analyzed by MTS assay and colony formation assay, and western blot assay was used to examine protein expression. Migration, invasion, and reporter assays were also carried out to study the regulations of TGF alpha in colon cancer. Our results evidenced that expression of TGF alpha facilitates short-term and long-term proliferations of colon cancer cells. Moreover, TGF alpha was suggested as a migration-and-invasion promoting factor of colon cancer. Finally, our data indicated that TGF alpha modulates epithelial-mesenchymal transition (EMT) markers and NF kappa B signaling pathway in colon cancer cells. We provide the first time evidence of the promoting role TGF alpha plays in colon cancer tumorigenesis with proposed regulatory mechanisms involving EMT alteration and NF kappa B signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.