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Review

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

1
Department of Science, University of Basilicata, viale dell’Ateneo Lucano 10, 85100 Potenza, Italy
2
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, via Orabona 4, 70125 Bari, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 68; https://doi.org/10.3390/cancers12010068
Received: 27 November 2019 / Revised: 20 December 2019 / Accepted: 23 December 2019 / Published: 25 December 2019
(This article belongs to the Special Issue Liver Cancer and Potential Therapeutic Targets)
Hepatocellular carcinoma (HCC) is a common malignancy. Despite progress in treatment, HCC is still one of the most lethal cancers. Therefore, deepening molecular mechanisms underlying HCC pathogenesis and development is required to uncover new therapeutic strategies. Metabolic reprogramming is emerging as a critical player in promoting tumor survival and proliferation to sustain increased metabolic needs of cancer cells. Among the metabolic pathways, the tricarboxylic acid (TCA) cycle is a primary route for bioenergetic, biosynthetic, and redox balance requirements of cells. In recent years, a large amount of evidence has highlighted the relevance of the TCA cycle rewiring in a variety of cancers. Indeed, aberrant gene expression of several key enzymes and changes in levels of critical metabolites have been observed in many solid human tumors. In this review, we summarize the role of the TCA cycle rewiring in HCC by reporting gene expression and activity dysregulation of enzymes relating not only to the TCA cycle but also to glutamine metabolism, malate/aspartate, and citrate/pyruvate shuttles. Regarding the transcriptional regulation, we focus on the link between NF-κB-HIF1 transcriptional factors and TCA cycle reprogramming. Finally, the potential of metabolic targets for new HCC treatments has been explored. View Full-Text
Keywords: tricarboxylic acid (TCA) cycle rewiring; metabolic reprogramming; hepatocellular carcinoma (HCC); malate/aspartate shuttle (MAS); citrate/pyruvate shuttle; glutamine; NF-κB; HIF1 tricarboxylic acid (TCA) cycle rewiring; metabolic reprogramming; hepatocellular carcinoma (HCC); malate/aspartate shuttle (MAS); citrate/pyruvate shuttle; glutamine; NF-κB; HIF1
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MDPI and ACS Style

Todisco, S.; Convertini, P.; Iacobazzi, V.; Infantino, V. TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma. Cancers 2020, 12, 68. https://doi.org/10.3390/cancers12010068

AMA Style

Todisco S, Convertini P, Iacobazzi V, Infantino V. TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma. Cancers. 2020; 12(1):68. https://doi.org/10.3390/cancers12010068

Chicago/Turabian Style

Todisco, Simona, Paolo Convertini, Vito Iacobazzi, and Vittoria Infantino. 2020. "TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma" Cancers 12, no. 1: 68. https://doi.org/10.3390/cancers12010068

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