The Role of Lysine Tyrosylquinone Containing Oxidases in Progression of Solid Tumors
2025
Tatyana V. Korneenko | Nikolay B. Pestov | Nickolai A. Barlev
Lysine tyrosylquinone (LTQ), the cofactor formed through copper-assisted tyrosine oxidation and subsequent intramolecular cross-linking, is inherent in all members of the lysyl oxidase family. Lysyl oxidases are unique among amine oxidases in that they maintain the LTQ coenzyme in a relatively surface-exposed position, making it accessible for the oxidative deamination of lysine side chains in various proteins, especially in the extracellular matrix. This process facilitates the formation of intramolecular cross-links, which are vital for the normal development of skin, bones, aorta, and other tissues. Unfortunately, in accordance with the antagonistic pleiotropy theory of aging, the enzyme activity that is essential in youth may become non-optimal throughout the lifespan. One consequence of excessive lysyl oxidase and its ectopic activity in the nucleus is the promotion of stiffness in solid tumors and increased survival of metastasizing cells. Therefore, LTQ-dependent oxidative deamination, especially at the stage of LTQ formation, is a promising druggable target for future combination therapies aimed at treating the most lethal cancers.
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