Drosophila melanogaster: A Model Organism to Study Cancer

Mirzoyan, Zhasmine; Sollazzo, Manuela; Allocca, Mariateresa; Valenza, Alice Maria; Grifoni, Daniela; Bellosta, Paola

doi:10.3389/fgene.2019.00051

Cited by 169 publications

(116 citation statements)

References 216 publications

(265 reference statements)

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“…Deregulated pH is now considered a hallmark of cancer with a higher pHi and a lower pHe observed in cancer cells as compared to normal cells [43]. Many tumor models have been described in Drosophila [44]. Overexpression of activated Ras (Ras V12 ) causes hyperplastic overgrowth [45] and metastatic behavior in combination with loss of polarity genes [27].…”

Section: Using Tphusion To Detect Clonal Ph Changesmentioning

confidence: 99%

tpHusion: An efficient tool for clonal pH determination in Drosophila

Gupta

Stocker

2020

PLoS ONE

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Genetically encoded pH indicators (GEpHI) have emerged as important tools for investigating intracellular pH (pHi) dynamics in Drosophila. However, most of the indicators are based on the Gal4/UAS binary expression system. Here, we report the generation of a ubiquitously-expressed GEpHI. The fusion protein of super ecliptic pHluorin and FusionRed was cloned under the tubulin promoter (tpHusion) to drive it independently of the Gal4/UAS system. The function of tpHusion was validated in various tissues from different developmental stages of Drosophila. Differences in pHi were also indicated correctly in fixed tissues. Finally, we describe the use of tpHusion for comparative analysis of pHi in manipulated clones and the surrounding cells in epithelial tissues. Our findings establish tpHusion as a robust tool for studying pHi in Drosophila.

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Section: Using Tphusion To Detect Clonal Ph Changesmentioning

confidence: 99%

tpHusion: An efficient tool for clonal pH determination in Drosophila

Gupta

Stocker

2020

PLoS ONE

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“…A wealth of fly studies has demonstrated that the mechanistic processes of retinogenesis are largely conserved across species, despite stark physiological differences between the compound and mammalian eye (reviewed in [9,66]). Further, its fully mapped genome shares 60% homology with humans, enabling this invertebrate model to aid the development of medical treatments for numerous neural disorders and diseases [67]. Most significantly, the model shares comparable microscale features in its developing visual system, despite large differences in adult eye size and configuration [66,68].…”

Section: Conserved Retinal Developmentmentioning

confidence: 99%

A Micro-Optic Stalk (μOS) System to Model the Collective Migration of Retinal Neuroblasts

et al. 2020

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Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes of replacement neural stem cells. The system scales with the microstructure of the Drosophila optic stalk, which is a pre-cursor to the optic nerve, to produce signaling fields spatially comparable to in vivo RNB stimuli. Experiments used the micro-optic stalk system, or μOS, to demonstrate the preferred sizing and directional migration of collective, motile RNB groups in response to changes in exogenous concentrations of fibroblast growth factor (FGF), which is a key factor in development. Our data highlight the importance of cell-to-cell contacts in enabling cell cohesion during collective RNB migration and point to the unexplored synergy of invertebrate cell study and microfluidic platforms to advance regenerative strategies.

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“…Cancer development is a multistep process that is driven by a heterogeneous combination of somatic mutations at the genetic and epigenetic levels [1,2]. Specific mutations in oncogenes [3] and tumor suppressor genes, [4,5] that result in their activation and inactivation, respectively, manifest themselves at tissue-level in the form of polyps, multi-layering, and metastasis [1,6,7]. These system-level properties resulting from heterogeneous biomolecular aberrations are also acclaimed as "hallmarks of cancer" [1,7].…”

Section: Introductionmentioning

confidence: 99%

In silico Drosophila Patient Model Reveals Optimal Combinatorial Therapies for Colorectal Cancer

Gondal

Butt

Shah

et al. 2020

Preprint

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In silico models of biomolecular regulation in cancer, annotated with patient-specific gene expression data can aid in the development of novel personalized cancer therapeutics strategies. Drosophila melanogaster is a well-established animal model that is increasingly being employed to evaluate preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining the Drosophila midgut epithelium and annotate them with patient-specific mutation data to develop an in silico Drosophila Patient Model (DPM). The network models were validated against cell-type-specific RNA-seq gene expression data from the FlyGut-seq database and through three literature-based case studies on colorectal cancer. The results obtained from the study help elucidate cell fate evolution in colorectal tumorigenesis, validate cytotoxicity of nine FDA-approved cancer drugs, and devise optimal personalized drug treatment combinations. The proposed personalized therapeutics approach also helped identify synergistic combinations of chemotherapy (paclitaxel) with targeted therapies (pazopanib, or ruxolitinib) for treating colorectal cancer. In conclusion, this work provides a novel roadmap for decoding colorectal tumorigenesis and in the development of personalized cancer therapeutics through a DPM.

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Drosophila melanogaster: A Model Organism to Study Cancer

Cited by 169 publications

References 216 publications

tpHusion: An efficient tool for clonal pH determination in Drosophila

tpHusion: An efficient tool for clonal pH determination in Drosophila

A Micro-Optic Stalk (μOS) System to Model the Collective Migration of Retinal Neuroblasts

In silico Drosophila Patient Model Reveals Optimal Combinatorial Therapies for Colorectal Cancer

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