Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy

Abstract

Elevated glycolysis remains a universal and primary character of cancer metabolism, which deeply depends on dysregulated metabolic enzymes. Lactate dehydrogenase A (LDHA) facilitates glycolytic process by converting pyruvate to lactate. Numerous researches demonstrate LDHA has an aberrantly high expression in multiple cancers, which is associated with malignant progression. In this review, we summarized LDHA function in cancer research. First, we gave an introduction of structure, location, and basic function of LDHA. Following, we discussed the transcription and activation mode of LDHA. Further, we focused on the function of LDHA in cancer bio-characteristics. Later, we discussed the clinical practice of LDHA in cancer prevention and treatment. What we discussed gives a precise insight into LDHA especially in cancer research, which will contribute to exploring cancer pathogenesis and its handling measures.

Keywords: LDHA; cancer; glycolysis; lactate; metabolism.

Figure 1

Regulation modes of LDHA. LDHA can be regulated in almost every step of gene expression. Methylation modification could repress LDHA transcription; various transcription factors can function at respective elements in LDHA promoter to activate or curb LDHA transcription; many kinds of microRNAs can bind to mRNA of LDHA to hinder its translation or induce degradation; phosphorylation can activate LDHA, while acetylation triggers its degradation by proteasome. AP‐1, activator protein‐1; CREB, cAMP response element‐binding protein; FOXM1, forkhead box protein M1; HIF‐1, hypoxia‐inducible factor‐1; HSF1, heat‐shock factor 1; KLF4, Kruppel‐like factor 4; TF, transcription factor

Figure 2

LDHA plays critical roles in hallmarks of cancer. LDHA is closely related to malignant bio‐characteristics of cancer via various mechanisms. LDHA can promote cancer cell proliferation and maintain cell survival; LDHA helps enhance cancer cell invasion and metastasis; LDHA can also trigger angiogenesis; LDHA can assist cancer cells in immune escape. ATP, adenosine triphosphate; CSCs, cancer stem cells; EMT, epithelial‐to‐mesenchymal; IL‐8, interleukin‐8; MDSCs, myeloid‐derived suppressor cells; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor