Drosophila as a toolkit to tackle cancer and its metabolism

Jiang, Hui; Kimura, Tatsuo; Han, Hugang; Yamamura, Ryodai; Sonoshita, Masahiro

doi:10.3389/fonc.2022.982751

Cited by 8 publications

(6 citation statements)

References 166 publications

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“…Among the animal cancer models, the common fruit fly is emerging as a precious resource for cancer biology and metabolic studies [ 65 ], since it offers a valuable toolkit with various advantages including high genetic conservation of major metabolic and cancer pathways and similar drug response to mammals.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila

Pilesi,

Tesoriere,

Ferriero

et al. 2024

Cell Death Dis

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Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5’-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign RasV12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgllPNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that RasV12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding RasV12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in RasV12DlgRNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.

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Section: Discussionmentioning

confidence: 99%

Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila

Pilesi,

Tesoriere,

Ferriero

et al. 2024

Cell Death Dis

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“…D. melanogaster has several advantages over other models, including low gene redundancy and well-established gene manipulation techniques. Multiple complex D. melanogaster cancer phenotypes have been successfully generated, covering various types of cancers, such as colorectal cancer, thyroid cancer, brain cancer, and LC [23]. D. melanogaster models with variants of genes, such as EGFR, KRAS, RAF, and ALK, have all been established in the field of LC [23].…”

Section: Drosophila Melanogastermentioning

confidence: 99%

“…Multiple complex D. melanogaster cancer phenotypes have been successfully generated, covering various types of cancers, such as colorectal cancer, thyroid cancer, brain cancer, and LC [23]. D. melanogaster models with variants of genes, such as EGFR, KRAS, RAF, and ALK, have all been established in the field of LC [23]. D. melanogaster has been extensively used to study cancer signaling cascades, such as WNT, HIPPO, JAK/STAT, RAS, NOTCH, HEDGEHOG, BMP, and TGF-β pathways [24].…”

Section: Drosophila Melanogastermentioning

confidence: 99%

Zebrafish in Lung Cancer Research

Wu,

Hua,

et al. 2023

Cancers

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Zebrafish is increasingly used as a model organism for cancer research because of its genetic and physiological similarities to humans. Modeling lung cancer (LC) in zebrafish has received significant attention. This review focuses on the insights gained from using zebrafish in LC research. These insights range from investigating the genetic and molecular mechanisms that contribute to the development and progression of LC to identifying potential drug targets, testing the efficacy and toxicity of new therapies, and applying zebrafish for personalized medicine studies. This review provides a comprehensive overview of the current state of LC research performed using zebrafish, highlights the advantages and limitations of this model organism, and discusses future directions in the field.

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“…In addition, fruit flies can also serve as models for epithelial cancers, including colorectal cancers (CRC). Due to physiological and morphological similarities between fruit flies and mammals, the fly gut, particularly the midgut, is useful for studying the contributions of signaling pathways and metabolism in CRC ( Jiang et al., 2022 ). Recurrent mutations in CRC have been modeled in flies, and multigenic fly models have been developed to unravel the complexity of CRC in terms of metabolism and drug response.…”

Section: Microbial Interactions In Drosophila Modu...mentioning

confidence: 99%

Drosophila melanogaster as a model to study polymicrobial synergy and dysbiosis

Cao,

Scoffield,

Xie

et al. 2023

Front. Cell. Infect. Microbiol.

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The fruit fly Drosophila melanogaster has emerged as a valuable model for investigating human biology, including the role of the microbiome in health and disease. Historically, studies involving the infection of D. melanogaster with single microbial species have yielded critical insights into bacterial colonization and host innate immunity. However, recent evidence has underscored that multiple microbial species can interact in complex ways through physical connections, metabolic cross-feeding, or signaling exchanges, with significant implications for healthy homeostasis and the initiation, progression, and outcomes of disease. As a result, researchers have shifted their focus toward developing more robust and representative in vivo models of co-infection to probe the intricacies of polymicrobial synergy and dysbiosis. This review provides a comprehensive overview of the pioneering work and recent advances in the field, highlighting the utility of Drosophila as an alternative model for studying the multifaceted microbial interactions that occur within the oral cavity and other body sites. We will discuss the factors and mechanisms that drive microbial community dynamics, as well as their impacts on host physiology and immune responses. Furthermore, this review will delve into the emerging evidence that connects oral microbes to systemic conditions in both health and disease. As our understanding of the microbiome continues to evolve, Drosophila offers a powerful and tractable model for unraveling the complex interplay between host and microbes including oral microbes, which has far-reaching implications for human health and the development of targeted therapeutic interventions.

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Drosophila as a toolkit to tackle cancer and its metabolism

Cited by 8 publications

References 166 publications

Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila

Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila

Zebrafish in Lung Cancer Research

Drosophila melanogaster as a model to study polymicrobial synergy and dysbiosis

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