TMED3 and malignant colon neoplasm: 2- The self-sustaining local, anti-metastatic WNT-TCF loop in colon cancer cells is proposed to rebalance in favor of pro-metastatic TMED9, CNIH4, TGFα, GLI signaling during the metastatic transition, which involves WNT signaling repression (e.g., WNT ligand and TMED3 downregulation) and the enhancement of the expression levels and function of TMED9, CNIH4, TGFA, and GLI1 (Fig. 8j).