Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology.

IF 3.1 Q2 PHARMACOLOGY & PHARMACY
Advanced pharmaceutical bulletin Pub Date : 2024-10-01 Epub Date: 2024-06-22 DOI:10.34172/apb.2024.049
Maher Monir Akl, Amr Ahmed
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引用次数: 0

Abstract

The Warburg effect, first observed by Otto Warburg in the 1920s, delineates a metabolic phenomenon in which cancer cells exhibit heightened glucose uptake and lactate production, even under normoxic conditions. This metabolic shift towards glycolysis, despite the presence of oxygen, fuels the energy demands of rapidly proliferating cancer cells. Dysregulated glucose metabolism, characterized by the overexpression of glucose transporters and the redirection of metabolic pathways towards glycolysis, lies at the crux of this metabolic reprogramming. Consequently, the accumulation of lactate as a byproduct contributes to the creation of an acidic tumor microenvironment, fostering tumor progression and metastasis. However, recent research, notably proposed by Maher Akl, introduces a novel perspective regarding the role of glycolipids in cancer metabolism. Akl's glucolipotoxicity hypothesis posits that aberrant glycolipid metabolism, specifically the intracellular buildup of glycolipids, significantly influences tumor initiation and progression. This hypothesis underscores the disruptive impact of accumulated glycolipids on cellular homeostasis, thereby activating oncogenic pathways and promoting carcinogenesis. This perspective aims to synthesize the intricate mechanisms underlying both the Warburg effect and glucolipotoxicity, elucidating their collective contributions to tumor growth and malignancy. By comprehensively understanding these metabolic aberrations, novel avenues for therapeutic intervention targeting the fundamental drivers of cancer initiation and progression emerge, holding promise for more efficacious treatment strategies in the future.

探索癌症发展过程中沃伯格效应与糖脂毒性之间的相互作用:癌症病因学的新视角
沃伯格效应是奥托-沃伯格在 20 世纪 20 年代首次观察到的,它描述了一种新陈代谢现象,即即使在常氧条件下,癌细胞也会表现出更高的葡萄糖摄取量和乳酸生成量。尽管存在氧气,这种向糖酵解的代谢转变仍能满足快速增殖的癌细胞的能量需求。以葡萄糖转运体过度表达和代谢途径转向糖酵解为特征的葡萄糖代谢失调是这种代谢重编程的关键所在。因此,作为副产品的乳酸盐的积累有助于形成酸性的肿瘤微环境,促进肿瘤的进展和转移。不过,最近的研究,特别是马希尔-阿克勒(Maher Akl)提出的研究,为糖脂在癌症代谢中的作用引入了一个新的视角。Akl 的糖脂毒性假说认为,糖脂代谢异常,特别是糖脂在细胞内的堆积,对肿瘤的发生和发展有重大影响。这一假说强调了积累的糖脂对细胞稳态的破坏性影响,从而激活致癌途径并促进癌变。这一观点旨在综合沃伯格效应和糖脂毒性的复杂机制,阐明它们对肿瘤生长和恶性肿瘤的共同作用。通过全面了解这些代谢畸变,我们将发现针对癌症发生和发展的基本驱动因素进行治疗干预的新途径,为未来制定更有效的治疗策略带来希望。
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来源期刊
Advanced pharmaceutical bulletin
Advanced pharmaceutical bulletin PHARMACOLOGY & PHARMACY-
CiteScore
6.80
自引率
2.80%
发文量
51
审稿时长
12 weeks
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