Lysine succinylation functions as a metabolic and epigenetic regulator in cancer development and therapy

Lysine succinylation is a post-translational modification (PTM) that is prevalent in organisms. This process involves transferring a succinyl group to a specific residue of a target protein, thereby playing a role in various cellular processes. The modification is critically involved in diverse physiological and pathological processes, including tumorigenesis, progression, and prognosis, and it is also closely linked to cancer diagnosis and therapeutic strategies. Recently, there has been a growing number of studies on the relationship between tumors and lysine succinylation. Current evidence indicates that lysine succinylation can remodel cancer cell metabolism by altering the structure or activity of metabolism-related proteins. Notably, research has revealed that lysine succinylation has a dual role in tumorigenesis: the hyper-succinylation of specific proteins in different tumor types may either promote or suppress cancer progression. This article aims to comprehensively review the regulatory mechanisms and functional roles of protein succinylation in tumors. It systematically summarizes the fundamental characteristics and regulatory enzymes of lysine succinylation, with a focus on different patterns of this modification across various types of cancer and the underlying mechanisms of its downstream signaling pathways. These findings highlight its potential implications for novel diagnostic strategies and therapeutic targets in cancer.