Drosophila and the Hallmarks of Cancer

Abstract

: 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.

A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in Drosophila

“…The majority of tumors arising in these epithelial tissues display disrupted cell polarity ( Martinez et al, 2009 ), which was confirmed using the cell adhesion marker Armadillo ( Figure 1—figure supplement 1D–E ). Additionally, we observed ectopic expression of Matrix metalloprotease 1 (MMP1) ( Figure 1—figure supplement 1F–G ), which is required for matrix degradation and the invasive potential of tumor cells ( Christofi and Apidianakis, 2013 ; Uhlirova and Bohmann, 2006 ).…”

Aging and the clock: Perspective from flies to humans

“…The cost‐effectiveness, genetic tractability, high throughput assays and availability of tools to manipulate neuronal properties with spatiotemporal accuracy of Drosophila have propelled it to the forefront as a competitive model for rapid identification of the cellular and molecular mechanisms underlying aging‐related diseases including neurodegenerative diseases (Blake et al., ; Gerstner et al., ; Krishnan, Kretzschmar, Rakshit, Chow & Giebultowicz, ); cardiovascular diseases (Piazza & Wessells, ; Yu, Daniels, Glaser & Wolf, ; Zarndt et al., ), cancer (Christofi & Apidianakis, ; Rudrapatna, Cagan & Das, ); diabetes and obesity (Alfa & Kim, ; Park et al., ; Trinh & Boulianne, ). As a model, Drosophila has also been used for evaluating the efficacy of potential therapeutic drugs to treat aging‐related diseases and disorders (Das & Cagan, ; Palandri et al., ).…”

Intercellular Cooperation and Competition in Brain Cancers: Lessons FromDrosophilaand Human Studies

“…The molecular mechanisms that induce intercellular signals leading to compensatory proliferation remain elusive. Nonetheless, taking advantage of several genetic mosaic models in Drosophila , the nature of some signals underlying these interactions is beginning to emerge [4, 19, 20]. In general, apoptotic clones are unable to induce effector caspases (termed “undead cells”) and continue to secrete proliferation signals (e.g., morphogens such as Wingless, transforming growth factor‐β, or Hedgehog) to the neighboring oncogenic clones.…”

“…Complex signaling interactions between cancer cells and their microenvironment and the cooperation or competition between heterogeneous cancer clones contribute to tumorigenesis and malignant transformation. Given these complexities, Drosophila has proved to be an excellent, if not the perfect, model for cancer studies, not only because of its rich history as a genetic model and the conservation of genetic and cell biological processes from flies to humans, but also because of the arsenal of genetic tools and techniques available for study in flies [2,[18][19][20]. Similar to human cancers, Drosophila cancers can invade and breach the extracellular matrix, recruit stromal cells, and metastasize to other organs [2,[21][22][23].…”