Mito-Nuclear Communication in Hepatocellular Carcinoma Metabolic Rewiring

Mello, Tommaso; Simeone, Irene; Galli, Andrea

doi:10.3390/cells8050417

Cited by 27 publications

(20 citation statements)

References 263 publications

(328 reference statements)

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“…There is evidence supporting constituent elements of the theory presented here at the cellular and molecular levels, particularly with regard to the interplay between mitochondria and nucleus. For example, a number of studies show that when the communication between mitochondria and the nucleus fails, mitochondria become dysfunctional, and tumorigenesis can be triggered [15,16,17,18]. This evidence is emphasized by the importance of mito–nuclear communications in human cancer, as demonstrated by recent findings showing an increased somatic transfer of mitochondrial DNA (mtDNA) in colorectal tumors [19].…”

Section: Further Explanationsmentioning

confidence: 99%

The Systemic–Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System

Mazzocca

2019

IJMS

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The Systemic–Evolutionary Theory of Cancer (SETOC) is a recently proposed theory based on two important concepts: (i) Evolution, understood as a process of cooperation and symbiosis (Margulian-like), and (ii) The system, in terms of the integration of the various cellular components, so that the whole is greater than the sum of the parts, as in any complex system. The SETOC posits that cancer is generated by the de-emergence of the “eukaryotic cell system” and by the re-emergence of cellular subsystems such as archaea-like (genetic information) and/or prokaryotic-like (mitochondria) subsystems, featuring uncoordinated behaviors. One of the consequences is a sort of “cellular regression” towards ancestral or atavistic biological functions or behaviors similar to those of protists or unicellular organisms in general. This de-emergence is caused by the progressive breakdown of the endosymbiotic cellular subsystem integration (mainly, information = nucleus and energy = mitochondria) as a consequence of long-term injuries. Known cancer-promoting factors, including inflammation, chronic fibrosis, and chronic degenerative processes, cause prolonged damage that leads to the breakdown or failure of this form of integration/endosymbiosis. In normal cells, the cellular “subsystems” must be fully integrated in order to maintain the differentiated state, and this integration is ensured by a constant energy intake. In contrast, when organ or tissue damage occurs, the constant energy intake declines, leading, over time, to energy shortage, failure of endosymbiosis, and the de-differentiated state observed in dysplasia and cancer.

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Section: Further Explanationsmentioning

confidence: 99%

The Systemic–Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System

Mazzocca

2019

IJMS

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“…Cancer cells tend to have an altered energy metabolism, known as the Warburg effect, that is characterized by a higher glucose uptake and glycolysis rather than oxidative phosphorylation . The Warburg effect has been widely examined in human cancers, including HCC, and is closely associated with the aggressiveness and high proliferation of the cancer . Lactate dehydrogenase (LDHA) has been reported to be a critical enzyme involved in glycolysis and proliferation in HCC .…”

Section: Introductionmentioning

confidence: 99%

Xanthophyll β‐Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet–Promoted Hepatocellular Carcinoma Progression in Mice

Lim

et al. 2020

Molecular Nutrition Food Res

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Scope: -Cryptoxanthin (BCX) can be cleaved by both -carotene 15,15′-oxygenase (BCO1) and -carotene 9′,10′-oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)-initiated, highly refined carbohydrate diet (HRCD)-promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity. Methods and results: Two-week-old male wild-type (WT) and BCO1 −/− /BCO2 −/− double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg −1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia-inducible factor-1 in tumors. Conclusion: This study suggests that BCX feeding may alleviate HRCD-promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.

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“…It has been described that all members of the MYB family, including c-MYB, interact with pVHL [37]. B-MYB is also targeted by pVHL for degradation via the proteasome [19,81,82]. Altogether, these results suggest that the absence of pVHL is needed to achieve an appropriately regulated expression of c-MYB, which is a key factor involved in the MYBBP1A downregulation response.…”

Section: Vhl the Third Playermentioning

confidence: 80%

The Tumor Suppressor Roles of MYBBP1A, a Major Contributor to Metabolism Plasticity and Stemness

Felipe‐Abrio

Carnero

2020

Cancers

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The MYB binding protein 1A (MYBBP1A, also known as p160) acts as a co-repressor of multiple transcription factors involved in many physiological processes. Therefore, MYBBP1A acts as a tumor suppressor in multiple aspects related to cell physiology, most of them very relevant for tumorigenesis. We explored the different roles of MYBBP1A in different aspects of cancer, such as mitosis, cellular senescence, epigenetic regulation, cell cycle, metabolism plasticity and stemness. We especially reviewed the relationships between MYBBP1A, the inhibitory role it plays by binding and inactivating c-MYB and its regulation of PGC-1α, leading to an increase in the stemness and the tumor stem cell population. In addition, MYBBP1A causes the activation of PGC-1α directly and indirectly through c-MYB, inducing the metabolic change from glycolysis to oxidative phosphorylation (OXPHOS). Therefore, the combination of these two effects caused by the decreased expression of MYBBP1A provides a selective advantage to tumor cells. Interestingly, this only occurs in cells lacking pVHL. Finally, the loss of MYBBP1A occurs in 8%–9% of renal tumors. tumors, and this subpopulation could be studied as a possible target of therapies using inhibitors of mitochondrial respiration.

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Mito-Nuclear Communication in Hepatocellular Carcinoma Metabolic Rewiring

Cited by 27 publications

References 263 publications

The Systemic–Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System

The Systemic–Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System

Xanthophyll β‐Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet–Promoted Hepatocellular Carcinoma Progression in Mice

The Tumor Suppressor Roles of MYBBP1A, a Major Contributor to Metabolism Plasticity and Stemness

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