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.

Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer.

The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy.