Discovery of a novel alpha isoform of the long-known enzyme LDHA provides new insights into cancer research

Abstract

Lactate dehydrogenase A is a key enzyme in energy metabolism, with significant roles in cancer progression. Huang et al. identified LDHAα, a novel LDHA isoform derived from an alternative transcript initiated at AUG198, producing a protein 3 kDa larger than canonical LDHA. LDHAα exhibits enhanced glycolytic activity and promotes glucose uptake, lactate production, and tumor growth more effectively than LDHA. Regulated by c-MYC and FOXM1, LDHAα is mainly cytoplasmic and serves as a potential cancer biomarker and therapeutic target. These findings highlight LDHAα's unique role in cancer metabolism and its potential for advancing targeted cancer therapies. © 2025 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.