The crucial role of CEMIP in cancer metastasis: Mechanistic insights and clinical implications.

Cancer metastasis is the leading cause of cancer-related deaths, making early detection and the prevention of metastatic progression critical research priorities. Recent studies have expanded our understanding of CEMIP (KIAA1199, HYBID), revealing its involvement in cancer metastasis and its potential role in slowing cancer progression. CEMIP plays critical roles in several stages of cancer metastasis: First, CEMIP promotes cancer cell proliferation to maintain cell heterogeneity before the metastasis process. Second, it facilitates cancer cell detachment by promoting the epithelial-mesenchymal transition (EMT) through alterations in signaling pathways. Third, CEMIP contributes to cancer cell adherence and attachment by enabling cells to withstand cell death (anoikis and ferroptosis) and hypoxia. Fourth, during the invasion process, CEMIP induces hyaluronan depolymerization and further modulates signaling to promote EMT. Lastly, in the pre-metastatic niche, CEMIP influences the tumor microenvironment through hypoxia, angiogenesis, signaling pathway changes, and hyaluronan degradation. Recent studies have focused on leveraging CEMIP as a diagnostic tool or a predictor of metastasis and/or targeting CEMIP to overcome cancer resistance and progression. This review aims to explore the role of CEMIP at each stage of cancer metastasis and highlight recent advances in targeting CEMIP to inhibit cancer progression.