Work

LDHA Lactylation Drives Malignant Progression of Oral Squamous Cell Carcinoma via a Positive Feedback Loop with Lactate

Year: 2026

Type: article

Abstract: analyses collectively illustrated that LDHA-K318 lactylation functions as a crucial driver of OSCC malignant progression. Functionally, our investigations revealed that the LDHA-K318R mutation diminishes lactate generation and decreases global protein Kla levels. GCN5 acts as an upstream "writer" that coordinately regulates LDHA-Kla, thereby modulating lactate production and facilitating OSCC malignancy. Furthermore, we identified HDAC1 as an "eraser" that governs LDHA-Kla status. Combined administration of the GCN5 inhibitor MB-3 and the LDHA-K318 lactylation-targeting peptide (K318-pe) remarkably inhibited tumor growth in the PDX models. Our study uncovers a positive feedback loop linking lactate and glycolysis, mediated by LDHA-Kla in OSCC. This discovery implicates lactylation-associated regulators as viable therapeutic targets, opening novel perspectives for clinical application.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.136949