Immune response to bacteria induces dissemination of Ras‐activated <i>Drosophila</i> hindgut cells

Bangi, Erdem; Pitsouli, Chrysoula; Rahme, Laurence G.; Cagan, Ross L.; Apidianakis, Yiorgos

doi:10.1038/embor.2012.44

Cited by 48 publications

(65 citation statements)

References 29 publications

(52 reference statements)

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“…These cells overproliferate and invade basally where they migrate away through the activation of E-cadherin, Rho1, JNK, and MMPs. These metastatic properties have also been observed in our study of the intestinal hindgut cells where we investigated the JNK-mediated dissemination and MMP1 expression of hindgut enterocytes in the abdominal cavity through visualization of the hindgut enterocyte marker byn-GAL4-UAS-GFP [92]. In an effort to find genetic modifiers from lethal (3) malignant mediated brain tumor, germline fitness genes were found through ectopic expression to induce tumor formation, invasion, and metastasis via a soma to germline transformation [152].…”

Section: Invasion and Metastasismentioning

confidence: 77%

“…Drosophila studies demonstrate this notion by inducing inflammatory responses through bacterial infection leading to the intestinal stem-cell-mediated compensatory proliferation in the midgut or hindgut cell invasion and dissemination in the abdominal cavity [55,92]. These and other fly models showing oncogene and polarity gene loss synergism in tumor growth and invasion in Drosophila larvae [77] utilize genetic manipulation of oncogenes and tumor suppressor genes to promote disease phenotypes.…”

Section: Modeling Cancer At the Organism Levelmentioning

confidence: 94%

“…Interestingly, oncogenic hindgut enterocytes and progenitors cooperate with bacterially induced immune response to invade basally the epithelium via MMP1 expression, extracellular matrix destruction, and dissemination into the abdominal cavity [92]. This invasion and dissemination is controlled by the Imd and JNK pathways induced by the bacteria in cooperation with the RasV12 oncogene.…”

Section: Tumor and Metastasis Promoting Inflammation: Infectionmentioning

confidence: 98%

“…These and other fly models showing oncogene and polarity gene loss synergism in tumor growth and invasion in Drosophila larvae [77] utilize genetic manipulation of oncogenes and tumor suppressor genes to promote disease phenotypes. Importantly, genetic predisposition can synergize with immune responses such as infection and inflammation to induce stem cell tumors as well as invasion and migration [55,92]. Various pathways that control cell growth, proliferation, and apoptosis can also be studied through these mutant phenotypes.…”

Section: Modeling Cancer At the Organism Levelmentioning

confidence: 99%

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Drosophila and the Hallmarks of Cancer

Christofi

Apidianakis

2013

Advances in Biochemical Engineering/Biotechnology

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: Cancer was the disease of the twentieth century. Today it is still a leading cause of death worldwide despite being intensively investigated. Abundant knowledge exists regarding the pathological and molecular mechanisms that drive healthy cells to become malignant and form metastatic tumors. The relation of oncogenes and tumor suppressors to the genetic trigger of carcinogenesis is unquestionable. However, the development of the disease requires many characteristics that due to their proven role in cancer are collectively described as the "hallmarks of cancer." We highlight here the historic discoveries made using the model organism Drosophila melanogaster and its contributions to biomedical and cancer research. Flies are utilized as a model organism for the investigation of each and every aspect of cancer hallmarks. Due to the significant conservation between flies and mammals at the signaling and tissue physiology level it is possible to explore the genes and mechanisms responsible for cancer pathogenesis in flies. Recent Drosophila studies suggest novel aspects of therapeutic intervention and are expected to guide cancer research in the twenty-first century.

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Section: Invasion and Metastasismentioning

confidence: 77%

Section: Modeling Cancer At the Organism Levelmentioning

confidence: 94%

Section: Tumor and Metastasis Promoting Inflammation: Infectionmentioning

confidence: 98%

Section: Modeling Cancer At the Organism Levelmentioning

confidence: 99%

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Drosophila and the Hallmarks of Cancer

Christofi

Apidianakis

2013

Advances in Biochemical Engineering/Biotechnology

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“…Drosophila are insects within the order Dipetera (flies) and used to investigate changes in the host genome and cellular signaling associated with IBD. Drosophila have a NF-K B signaling pathway similar to people and they produce NADPH oxidase dependent antibacterial reactive oxygen species (Bangi, Pitsouli, Rahme, Cagan, & Apidianakis, 2012). Both innate and adaptive immune responses can be assessed in fish.…”

Section: Considerations For Choosing the Most Appropriate Animal Modelmentioning

confidence: 99%

Considerations for Choosing Appropriate Animal Models to Study Inflammatory Bowel Disease

Uwiera¹,

Uwiera²,

Jiminez³

et al. 2016

JAS

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This article examines several animal models used to investigate mechanisms involved in the induction and progression of inflammatory bowel disease in people. The use of appropriate animal models to study intestinal inflammation requires careful consideration as each model has strengths and limitations for investigating disease, and no single model provides a complete understanding of the disease process. In as such, it compels researchers to carefully contemplate the advantages and disadvantages of each animal model, and to consider the process of choosing the best animal model(s) as an essential component of the experimental design.

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Modelling Cancer in Drosophila : The Next Generation

Cheng

Parsons

Richardson

2013

Encyclopedia of Life Sciences

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Drosophila melanogaster , the vinegar fly, has been utilised as a genetic amenable model organism for more than 100 years. In recent years, its use in modelling human cancer has been greatly expanding. In this article, an update of the recent advances in Drosophila research towards understanding cancer development is provided. Genetic analysis in Drosophila has provided considerable insight into the mechanisms controlling tissue growth and cell invasion/metastasis during tumourigenesis, as well as the importance of stem cells in tissue regeneration and cancer, and how genes cooperate in tumourigenesis. Several evolutionarily conserved signalling pathways are emerging as playing key roles in many of these processes, including the Jun kinase, Notch, Wnt, Jak/Stat and the Hippo tissue growth control pathway. Drosophila has also been specifically utilised to model certain human cancers, by expression of the human versions of cancer‐causing genes, including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia. Finally, the use of Drosophila as a vehicle for anticancer drug discovery is beginning to make an important impact in combating human cancer. Key Concepts: Drosophila is a useful system for modelling human cancer due to the high conservation of critical cancer‐causing genes between humans and flies. Many signalling pathways contribute to tissue growth; however, the Hippo growth control pathway is emerging as playing a major role. The Jun kinase signalling pathway plays a context‐dependent role in invasion/metastasis. Cell polarity and differentiation factors play important roles in controlling the behaviour of stem cells, which can be usurped in cancer. Cell competition mechanisms are important in removing damaged cells, and the perturbation of this control contributes to tumourigenesis. Cancer is a cooperative process and Drosophila research has revealed many cooperating oncogenes and tumour suppressors. Drosophila provides a useful model system to investigate specific human cancers including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia. Drosophila can be utilised to screen for anticancer drugs.

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Immune response to bacteria induces dissemination of Ras‐activated Drosophila hindgut cells

Cited by 48 publications

References 29 publications

Drosophila and the Hallmarks of Cancer

Drosophila and the Hallmarks of Cancer

Considerations for Choosing Appropriate Animal Models to Study Inflammatory Bowel Disease

Modelling Cancer in Drosophila : The Next Generation

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