Pyruvate Kinase M2 (PKM2) is a key glycolytic enzyme, which highly expressed in tumor cells, and plays a pivotal role in the growth, survival and metabolism reprogramming of cancer cells. Besides the location of cytoplasm as a glycolytic enzyme and the location of nucleus as a protein kinase, extracellular PKM2 is present in serum and feces of tumor patients. However, little is known about the secretion of PKM2 and its significance in the progression of colon cancer. Here we demonstrated that PKM2 could be secreted from colon cancer cells, and purified PKM2 protein mimicing the secreted PKM2 was able to promote colon cancer cell migration. Moreover, PI3K/Akt and Wnt/beta-catenin signaling were involved in secreted PKM2 induced colon cancer cell migration. The results reveal critical roles of secreted PKM2 in the progression of colon cancer, and indicate that PKM2 may be a therapeutic target for colon cancer. (C) 2015 Elsevier Inc. All rights reserved.