Spatio-temporal interactome of fructose-1,6-bisphosphate aldolase B in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent and aggressive form of malignancies with limited therapeutic options. Understanding the molecular mechanisms underlying HCC development and progression is crucial for the identification of novel therapeutic targets. Fructose-1,6-bisphosphate aldolase B (ALDOB) is a key enzyme in glycolysis which has been implicated in HCC pathogenesis. Metabolic reprogramming is a core hallmark of cancer, and downregulation of ALDOB in HCC leads to alterations in glucose metabolism. Our previous studies identified multiple enzymatic and non-enzymatic roles of ALDOB in HCC through protein-protein interactions in different cellular locations including cytosol and nucleus. In this study, to better understanding the precise role and the network of interacting proteins of ALDOB in HCC, we aim to reveal the potential regulatory mechanisms of ALDOB in HCC through a combination of proteomics and metabolomics. By performing subcellular proteome fractions and combine with APEX proximity labeling, we identified the ALDOB function in nuclear of different cell stage and conditions. To be more comprehensively understand the underlying pathway and mechanism, we possess RNA-seq to identify how ALDOB functional units associated pathways. We propose to perform comprehensive analyses to identify proteins that physically interact with ALDOB and their dynamic changes under various biological stimuli and across different stages of HCC, shedding light on its functional associations and molecular pathways in liver cancer in an attempt to enhance the understanding of HCC biology. This project will lay the ground for developing novel therapeutic strategies targeting ALDOB and its interactors in the fight against this deadly disease.