Review Article：

PCK1 dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities

Author: Jin Xiang ( 向进)，  Kai Wang， Ni Tang  

Abstract 摘要：

The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathway remodeling, enables tumor growth, progression, and metastasis. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key rate-limiting enzyme in gluconeogenesis, catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. PCK1 expression in gluconeogenic tissues is tightly regulated during fasting. In tumor cells, PCK1 is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular environment. Interestingly, PCK1 has an anti-oncogenic role in gluconeogenic organs (the liver and kidneys), but a tumor-promoting role in cancers arising from non-gluconeogenic organs. Recent studies have revealed that PCK1 has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic pathways. Aberrant PCK1 expression results in the activation of oncogenic pathways, accompanied by metabolic reprogramming, to maintain tumorigenesis. In this review, we summarize the mechanisms underlying PCK1 expression and regulation, and clarify the crosstalk between aberrant PCK1 expression, metabolic rewiring, and signaling pathway activation. In addition, we highlight the clinical relevance of PCK1 and its value as a putative cancer therapeutic target.

Keywords关键词：

Gluconeogenesis 糖异生, Cancer metabolism肿瘤代谢, Oncogenesis肿瘤发生, PCK1磷酸烯醇式丙酮酸羧激酶1, Tumor 

DOI:  https://doi.org/10.1016/j.gendis.2022.02.010 

Full text全文: https://www.sciencedirect.com/science/article/pii/S235230422200054X