The multifaceted roles of aldolase A in cancer: glycolysis, cytoskeleton, translation and beyond.

Cancer, a complicated disease characterized by aberrant cellular metabolism, has emerged as a formidable global health challenge. Since the discovery of abnormal aldolase A (ALDOA) expression in liver cancer for the first time, its overexpression has been identified in numerous cancers, including colorectal cancer (CRC), breast cancer (BC), cervical adenocarcinoma (CAC), non-small cell lung cancer (NSCLC), gastric cancer (GC), hepatocellular carcinoma (HCC), pancreatic cancer adenocarcinoma (PDAC), and clear cell renal cell carcinoma (ccRCC). Moreover, ALDOA overexpression promotes cancer cell proliferation, invasion, migration, and drug resistance, and is closely related to poor prognosis of patients with cancer. Although originally discovered to promote cancer initiation and progression by accelerating glycolysis, recent studies have revealed its atypical roles in cancer, e.g., adjusting cytoskeleton, regulating mRNA translation, cell signaling pathways, and DNA repair. These aforementioned findings challenge our traditional understanding of ALDOA function and prompt deep exploration of its novel roles in tumor biology. The present review summarizes the latest insights into ALDOA as a potential cancer biomarker and therapeutic target.