Cyclin E overexpression in the accessory gland induces tissue dysplasia.

The regulation of the cell division cycle is governed by a complex network of factors that together ensure that growing or proliferating cells maintain a stable genome. Defects in this system can lead to genomic instability that can affect tissue homeostasis and thus compromise human health. Variations in ploidy and cell heterogeneity are observed frequently in human cancers.

Insulin signaling mediates neurodegeneration in glioma.

Cell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is one of the most aggressive and frequent primary brain tumors.

Genome-Wide Screen for Context-Dependent Tumor Suppressors Identified Using in Vivo Models for Neoplasia in .

Genetic approaches in have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: the Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways.

Genomic instability and cancer: lessons from .

Cancer is a genetic disease that involves the gradual accumulation of mutations. Human tumours are genetically unstable. However, the current knowledge about the origins and implications of genomic instability in this disease is limited.

MicroRNAs in Drosophila Cancer Models.

MiRNAs are post-transcriptional regulators of gene expression which have been implicated in virtually all biological processes. MiRNAs are frequently dysregulated in human cancers. However, the functional consequences of aberrant miRNA levels are not well understood.

The miRNA regulates growth and tumorigenesis by repressing the cell cycle regulator .

One of the fundamental issues in biology is understanding how organ size is controlled. Tissue growth has to be carefully regulated to generate well-functioning organs, and defects in growth control can result in tumor formation. The Hippo signaling pathway is a universal growth regulator and has been implicated in cancer.

suppresses growth and tumor formation in .

Wnt/Wingless (Wg) signaling controls many aspects of animal development and is deregulated in different human cancers. The transcription factor dTcf/Pangolin (Pan) is the final effector of the Wg pathway in and has a dual role in regulating the expression of Wg target genes. In the presence of Wg, dTcf/Pan interacts with β-catenin/Armadillo (Arm) and induces the transcription of Wg targets.

Mechanisms of oncogenic cell competition-Paths of victory.

Cancer is a multistep process. In the early phases of this disease, mutations in oncogenes and tumor suppressors are thought to promote clonal expansion. These mutations can increase cell competitiveness, allowing tumor cells to grow within the tissue by eliminating wild type host cells.

Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer.

Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in a Drosophila model.

Oncogenic cooperation between Yorkie and the conserved microRNA in the wing disc of .

Tissue growth has to be carefully controlled to generate well-functioning organs. MicroRNAs are small non-coding RNAs that modulate the activity of target genes and play a pivotal role in animal development. Understanding the functions of microRNAs in development requires the identification of their target genes.

Yorkie and JNK Control Tumorigenesis in Drosophila Cells with Cytokinesis Failure.

Cytokinesis failure may result in the formation of polyploid cells, and subsequent mitosis can lead to aneuploidy and tumor formation. Tumor suppressor mechanisms limiting the oncogenic potential of these cells have been described. However, the universal applicability of these tumor-suppressive barriers remains controversial.

Drosophila as a Model to Study the Link between Metabolism and Cancer.

Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest new approaches to therapy. is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation.

The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in epithelia.

Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie () proto-oncogene, but not in tissue overexpressing epidermal growth factor receptor (EGFR).

Cancer in Drosophila: Imaginal Discs as a Model for Epithelial Tumor Formation.

Cancer genomics has greatly increased our understanding of the complexity of the genetic and epigenetic changes found in human tumors. Understanding the functional relationships among these elements calls for the use of flexible genetic models. We discuss the use of Drosophila models to study cooperation among genetic factors that contribute to disease progression.

Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation.

Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis.

Crosstalk between epithelial and mesenchymal tissues in tumorigenesis and imaginal disc development.

Background: Cancers develop in a complex mutational landscape. Interaction of genetically abnormal cancer cells with normal stromal cells can modify the local microenvironment to promote disease progression for some tumor types. Genetic models of tumorigenesis provide the opportunity to explore how combinations of cancer driver mutations confer distinct properties on tumors.

Oncogenic cooperation between SOCS family proteins and EGFR identified using a Drosophila epithelial transformation model.

MicroRNAs (miRNAs) are emerging as cooperating factors that promote the activity of oncogenes in tumor formation and disease progression. This poses the challenge of identifying the miRNA targets responsible for these interactions. In this study, we identify the growth regulatory miRNA bantam and its target, Socs36E, as cooperating factors in EGFR-driven tumorigenesis and metastasis in a Drosophila model of epithelial transformation.

Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control.

Background: The epidermal growth factor receptor (EGFR) and Hippo signaling pathways control cell proliferation and apoptosis to promote tissue growth during development. Misregulation of these pathways is implicated in cancer. Our understanding of the mechanisms that integrate the activity of these pathways remains fragmentary.

MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems.

Biological systems are continuously challenged by an environment that is variable. Yet, a key feature of developmental and physiological processes is their remarkable stability. This review considers how microRNAs contribute to gene regulatory networks that confer robustness.

The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing.

MicroRNAs (miRNAs) have been implicated in cell-cycle regulation and in some cases shown to have a role in tissue growth control. Depletion of miRNAs was found to have an effect on tissue growth rates in the wing primordium of Drosophila, a highly proliferative epithelium. Dicer-1 (Dcr-1) is a double-stranded RNAseIII essential for miRNA biogenesis.

Scarface, a secreted serine protease-like protein, regulates polarized localization of laminin A at the basement membrane of the Drosophila embryo.

Cell-matrix interactions brought about by the activity of integrins and laminins maintain the polarized architecture of epithelia and mediate morphogenetic interactions between apposing tissues. Although the polarized localization of laminins at the basement membrane is a crucial step in these processes, little is known about how this polarized distribution is achieved. Here, in Drosophila, we analyse the role of the secreted serine protease-like protein Scarface in germ-band retraction and dorsal closure-morphogenetic processes that rely on the activity of integrins and laminins.

Signalling molecules, growth regulators and cell cycle control in Drosophila.

During the development of a given organ or tissue within a multicellular organism, growth and patterning are controlled in a coordinated manner by the activity of a discrete number of signalling molecules and their corresponding pathways to give rise to a well-formed structure with a particular size, shape and pattern. Understanding how cells of different tissues or organs translate the activity of these pathways into an activation or repression of the cell cycle machinery in a context-dependent manner is at present one of the most intriguing questions in developmental and cancer biology. In this article we review the different roles of the Notch and Wingless signalling molecules in the regulation of cell cycle progression in the developing eye and wing imaginal discs of Drosophila and propose that, depending on how growth regulators are controlled in a context-dependent manner by the activity of these pathways, signalling molecules might have tumour suppressor or oncogene activity.

A Wingless and Notch double-repression mechanism regulates G1-S transition in the Drosophila wing.

The control of tissue growth and patterning is orchestrated in various multicellular tissues by the coordinated activity of the signalling molecules Wnt/Wingless (Wg) and Notch, and mutations in these pathways can cause cancer. The role of these molecules in the control of cell proliferation and the crosstalk between their corresponding pathways remain poorly understood. Crosstalk between Notch and Wg has been proposed to organize pattern and growth in the Drosophila wing primordium.