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Guangshun Sun,1,* Liangliang Wu,1,* Guoqiang Sun,1 Xuesong Shi,1 Hongyong Cao,1 Weiwei Tang2 1Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyong Cao; Weiwei Tang Email caohongy6167@163.com; 1243773473twww@sina.comAbstract: Despite the clinical development of new adjuvant and neoadjuvant chemotherapy drugs, colorectal cancer is still one of the leading causes of cancer-related death in human beings. WNT5a, an autocrine and paracrine β-catenin independent ligand, has been shown to induce tumor inhibition and carcinogenic signals, depending on the type of cancer. In patients with colorectal cancer, WNT5a triggers a variety of downstream signaling pathways, which mainly affect the migration and invasion of tumor cells. This article reviews the mechanism and therapeutic potential of WNT5a in colorectal cancer. In short, an in-depth understanding of the role of WNT5a in colorectal cancer is very helpful to better deal with this disease.Keywords: WNT5a, colorectal cancer, WNT, therapy