Pan-cancer perspectives on post-translational modifications and metastasis: Unraveling complex molecular mechanisms.

Metastasis is the leading cause of cancer death, due to complex molecular mechanisms. Post-translational modifications (PTMs) are essential in determining the function, structure, and interaction of proteins. Different steps of the metastatic cascade including the activation and rewiring of signaling pathways, epithelial to mesenchymal transition (EMT), cell migration and invasion, survival in the blood vessel, and colonization at a distance are modified by PTMs. Recent studies reveal that PTMs maintain the capacity of metastasis and phenotypic plasticity thus highlighting their essential role in metastasis biology. Even though the regulation mediated by PTMs is widely conserved, they are also tumor-type specific. Cancer metastasis is regulated by distinct patterns of enzymes and signaling pathways associated with PTMs, suggesting potential for diagnostic and therapeutic applications of PTM-based classification. In addition, widespread crosstalk between various classes of PTMs, whether cooperative or antagonistic, shapes regulatory networks that are multilayered and dynamic. The explanation of these regulatory mechanisms will enable the identification of critical control nodes, as well as provide a significant basis for developing PTM-informed anti-metastatic therapies.