Studies on human colon cancer gene APC by targeted expression in Drosophila

Bhandari, Poonam; Shashidhara, L.S.

doi:10.1038/sj.onc.1204849

Cited by 23 publications

(36 citation statements)

References 57 publications

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“…Moreover, such screens have provided a wealth of information to form heirarchies of gene function in signal transduction. Dominant phenotypes generated by a mammalian oncogene expressed in Drosophila can also be used in a modifier screen to reveal new genes involved in wellstudied signal transduction pathways, such as Wnt/wg signalling (Bhandari and Shashidhara, 2001). This report demonstrates that dosage modifier genetics in Drosophila can also be used to map out signal transduction pathways activated by an oncogenic RTK.…”

Section: Dosage Modifier Genetics Of Neu Signallingmentioning

confidence: 99%

Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model

et al. 2003

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Section: Dosage Modifier Genetics Of Neu Signallingmentioning

confidence: 99%

Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model

et al. 2003

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“…We had earlier reported a transgenic Drosophila model expressing human APC (hAPC) that enables functional studies on hAPC in a heterologous system (Bhandari and Shashidhara, 2001). We had reported that (i) misexpressed hAPC can suppress phenotypes associated with loss-of-function mutations in the Drosophila homologue of APC (dAPC1) and (ii) hAPC is able to suppress phenotypes induced by the overexpression of the activated or degradation-resistant form of Armadillo (ARM/b-catenin), the Drosophila homologue of b-catenin.…”

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confidence: 99%

“…Interestingly, hAPC when overexpressed in Drosophila imaginal discs sequesters ARM/b-catenin only in regions of active Wnt signaling (for example, dorsoventral boundary of wing imaginal discs), wherein activity levels of Shaggy (Sgg/GSK-3b; the Drosophila homologue of GSK-3b) are supposed to be the lowest. When both Sgg/ GSK-3b and hAPC are misexpressed together, human APC fails to sequester ARM/b-catenin (Bhandari and Shashidhara, 2001). This behavior has been validated in different genetic backgrounds of increased or decreased levels of Sgg/GSK-3b activity (Prasad et al, 2003;Bajpai et al, 2004).…”

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confidence: 99%

“…Arrowhead in f-j indicates the position of D/V boundary. UAS-hAPC/FL (full-length hAPC) and UAS-hAPC/CBD (comprises of residues from 959 to 1870 of hAPC) are reported in Bhandari and Shashidhara (2001). UAS-hAPC/MCR (comprises of only first 1315 residues of hAPC) was generated in this study.…”

mentioning

confidence: 99%

“…Interestingly, Drosophila and human APC share much less homology compared to Drosophila and human b-catenin (Bhandari and Shashidhara, 2001). Thus, our heterologous human APC misexpression system provides a convenient in vivo visual assay for observing specific interactions between overexpressed human APC and endogenous Drosophila ARM/b-catenin.…”

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Human APC sequesters β-catenin even in the absence of GSK-3β in a Drosophila model

2007

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There have been conflicting reports on the requirement of GSK-3b-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-a`-vis its ability to bind and degrade b-catenin. Using a unique combination of loss of function for Shaggy/GSK-3b and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/b-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3b activity, suggesting that sequestered Armadillo/b-catenin is non-functional. Based on these studies, we propose that binding per se of b-catenin by APC does not require phosphorylation by GSK-3b.

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Screening for Anti‐cancer Drugs inDrosophila

Richardson

Willoughby

Humbert

2015

Encyclopedia of Life Sciences

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The vinegar fly, Drosophila melanogaster, has been a cornerstone of genetic analysis and cell and developmental biology research for over 100 years. Within the last decade, Drosophila is making its mark in translational research in its utilisation in modelling human diseases and in screens for small molecule inhibitors. In particular, its use in modelling cancer development and in identifying anti‐cancer therapeutics is beginning to make an important contribution to the current drug discovery pipeline, which to date has been only poorly successful in delivering drugs, identified in vitro, into the clinic for anti‐cancer therapy. The primary advantages of the Drosophila system for use in anti‐cancer drug screening are the conservation of cancer genes/pathways between flies and mammals, its suitability for rapid phenotypic screening of chemicals for anti‐cancer effects in vivo in a high‐throughput and cost‐effective manner and its use in identifying drugs that can specifically target tumours in vivo . Key Concepts The current drug screening pipeline has been only poorly efficient in progressing anti‐cancer drugs to the clinic because of differences between in vitro and in vivo systems Drosophila melanogaster is an excellent model organism for cost‐effective high‐throughput in vivo screening for anti‐cancer compounds relevant to human cancer Drosophila larvae or adults can be readily screened in a high‐throughput manner for the effect of orally administered compounds on a particular phenotype using phenotypic or fluorescent read‐outs Drosophila models of cancer used for chemical screens include those generated by expression of cancer‐causing genes, whole animal synthetic lethality with radiation and specific cancer phenotypes Biological and technical limitations of Drosophila might restrict the discovery of compounds and their translation into the clinic Screening of orally administered drugs in flies has already proven to be successful in identifying new compounds or FDA‐approved compounds for use in cancer therapy

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Studies on human colon cancer gene APC by targeted expression in Drosophila

Cited by 23 publications

References 57 publications

Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model

Genetic identification of effectors downstream of Neu (ErbB-2) autophosphorylation sites in a Drosophila model

Human APC sequesters β-catenin even in the absence of GSK-3β in a Drosophila model

Screening for Anti‐cancer Drugs inDrosophila

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