Lactylation and Cuproptosis: Convergent and Divergent Regulatory Networks in Cancers and Degenerative Diseases
Year: 2026
Type: preprint
Abstract: Background: Lactylation and glycolytic reprogramming of TCA cycle proteins for epigenetic and proteomic reorganization to trigger cuproptosis, in human cancer and multisystem degenerative diseases are here reviewed. Convergent signaling axes of different types of cancer and of different types of multisystem degeneration are presented, as well as divergent disease-specific pathways. The goal of this review is to provide a theoretical framework for cross-disease precision medicine. Methods: This review retrieved relevant studies published from 2022 to 2026, and the search databases included PubMed, web of science, and Scopus. Results: This paper hierarchically combed the change characteristics of common and disease-specific signaling pathways in cancer and multisystem degenerative diseases. In human tumors, there is a general damage amplification pathway: this pathway relies on exosomes to transport lactated modified proteins, thereby achieving the transmission of paracrine signals. By lactylation, cancer cells become resistant to cuproptosis to allow for their survival. In contrast, cells of patients with multisystem degenerative diseases undergo copper-induced mitochondrial damage leading to irreversible tissue damage. Here, we contrast two opposing functions: exosomal transfer of lactylated proteins to reorganize the tumor environment and to spread copper toxicity to lesions of degenerative diseases. Conclusion: This review develops a unified “convergence-divergence” model for the two functions of lactylation. It proposes shared targets as well as subtype-specific therapeutic strategies for the two diseases. Finally, suitable translational biomarkers are screened, and an integrated framework for comparative precision medicine in the two fields of oncology and geriatric metabolic diseases is established.
Source: Preprints.org
Authors: Xiayu Wu, Xiangxu Kan, Shaotian Chen
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7207589756