PO.MCB09.02 · 分子与细胞生物学
果糖-1,6-二磷酸醛缩酶B在肝细胞癌中的时空互作组
Spatio-temporal interactome of fructose-1,6-bisphosphate aldolase B in hepatocellular carcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肝细胞癌(HCC)是一种常见且侵袭性的恶性肿瘤,治疗选择有限。理解HCC发生和进展的分子机制对于确定新型治疗靶点至关重要。果糖-1,6-二磷酸醛缩酶B(ALDOB)是糖酵解中的关键酶,已被证明参与HCC的发病机制。代谢重编程是癌症的核心标志,HCC中ALDOB的下调导致葡萄糖代谢的改变。我们既往的研究通过在包括胞质和细胞核在内的不同细胞位置的蛋白质-蛋白质相互作用,确定了ALDOB在HCC中的多种酶促和非酶促作用。在本研究中,为了更好地理解ALDOB在HCC中的确切作用及其互作蛋白网络,我们旨在通过蛋白质组学和代谢组学相结合的方法揭示ALDOB在HCC中的潜在调控机制。通过进行亚细胞蛋白质组分级并结合APEX邻近标记,我们在不同细胞阶段和条件下确定了ALDOB在细胞核中的功能。为了更全面地理解其潜在的通路和机制,我们运用RNA-seq确定ALDOB功能单元相关通路。我们拟进行全面分析,以确定与ALDOB发生物理相互作用的蛋白质及其在各种生物刺激下和HCC不同阶段中的动态变化,从而阐明其在肝癌中的功能关联和分子通路,力求加深对HCC生物学的理解。本项目将为开发针对ALDOB及其互作蛋白的新型治疗策略、对抗这一致命疾病奠定基础。
查看英文原文 English abstract
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.
利益披露 Disclosure
X. Chen, None..
H. Wang, None..
S. Zhong, None..
H. Yin, None.