Originally discovered as a hypothetical protein with unknown function, CEMIP (cell migration-inducing and hyaluronan-binding protein) has been implicated in the pathogenesis of numerous diseases, including deafness, arthritis, atherosclerosis, idiopathic pulmonary fibrosis, and cancer. Although a comprehensive definition of its molecular functions is still in progress, major functions ascribed to CEMIP include the depolymerization of the extracellular matrix component hyaluronic acid (HA) and the regulation of a number of signaling pathways. CEMIP is a promising biomarker for colorectal cancer. Its expression is associated with poor prognosis for patients suffering from colorectal and other types of cancer and functionally contributes to tumor progression and metastasis. Here, we review our current understanding of how CEMIP is able to foster the process of tumor growth and metastasis, focusing particularly on colorectal cancer. Studies in cancer cells suggest that CEMIP exerts its pro-tumorigenic and pro-metastatic activities through stimulating migration and invasion, suppressing cell death and promoting survival, degrading HA, regulating pro-metastatic signaling pathways, inducing the epithelial-mesenchymal transition (EMT) program, and contributing to the metabolic reprogramming and pre-metastatic conditioning of future metastatic microenvironments. There is also increasing evidence indicating that CEMIP may be expressed in cells within the tumor microenvironment that promote tumorigenesis and metastasis formation, although this remains in an early stage of investigation. CEMIP expression and activity can be therapeutically targeted at a number of levels, and preliminary findings in animal models show encouraging results in terms of reduced tumor growth and metastasis, as well as combating therapy resistance. Taken together, CEMIP represents an exciting new player in the progression of colorectal and other types of cancer that holds promise as a therapeutic target and biomarker.
Keywords: CEMIP; EMT; KIAA1199; hyaluronic acid; hyaluronidase; metastasis.