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Drosophila tumor

Bojie Cong, Shizue Ohsawa, Tatsushi Igaki
Epithelial cancer tissues often possess polyploid giant cells, which are thought to be highly oncogenic. However, the mechanisms by which polyploid giant cells are generated in tumor tissues and how such cells contribute to tumor progression remain elusive. We previously noticed in Drosophila imaginal epithelium that cells mutant for the endocytic gene rab5 exhibit enlarged nuclei. Here we find that mutations in endocytic 'neoplastic tumor-suppressor' genes, such as rab5, vps25, erupted, or avalanche result in generation of polyploid giant cells...
March 14, 2018: Oncogene
Cássio Resende de Morais, Ana Maria Bonetti, Alexandre Aparecido Mota, Carlos Fernando Campos, Henrique Nazareth Souto, Maria Paula Carvalho Naves, Vanessa Santana Vieira Santos, Edimar Olegário de Campos Júnior, Luiz Alfredo Pavanin, Alexandre Azenha Alves de Rezende, Mário Antônio Spanó, Boscolli Barbosa Pereira
Physico-chemical and toxicological analyses are of fundamental importance to determine water quality. The objectives of the present study were to evaluate the toxicity, mutagenicity and carcinogenicity of samples from the Mumbuca Stream and the Perdizes River, through both SMART and the wts test, respectively, in somatic cells of Drosophila melanogaster and to quantify the amount of heavy metals and other pollutants, which are indicative of environmental quality. Water samples were collected (M1, M2, P1, P2 and MP) and submitted to physico-chemical analysis, calculating the water quality index for each sampling site...
March 3, 2018: Chemosphere
Terrence Hanscom, Varandt Y Khodaverdian, Mitch McVey
In this chapter, we describe a method for the recovery and analysis of alternative end-joining (alt-EJ) DNA double-strand break repair junctions following I-SceI cutting in Drosophila melanogaster embryos. Alt-EJ can be defined as a set of Ku70/80 and DNA ligase 4-independent end-joining processes that are typically mutagenic, producing deletions, insertions, and chromosomal rearrangements more frequently than higher-fidelity repair pathways such as classical nonhomologous end joining or homologous recombination...
2018: Methods in Enzymology
Santiago Nahuel Villegas, Rita Gombos, Lucia García-López, Irene Gutiérrez-Pérez, Jesús García-Castillo, Diana Marcela Vallejo, Vanina Gabriela Da Ros, Esther Ballesta-Illán, József Mihály, Maria Dominguez
The PI3K/Akt signaling pathway, Notch, and other oncogenes cooperate in the induction of aggressive cancers. Elucidating how the PI3K/Akt pathway facilitates tumorigenesis by other oncogenes may offer opportunities to develop drugs with fewer side effects than those currently available. Here, using an unbiased in vivo chemical genetic screen in Drosophila, we identified compounds that inhibit the activity of proinflammatory enzymes nitric oxide synthase (NOS) and lipoxygenase (LOX) as selective suppressors of Notch-PI3K/Akt cooperative oncogenesis...
March 6, 2018: Cell Reports
Rémi-Xavier Coux, Felipe Karam Teixeira, Ruth Lehmann
Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. The tumor suppressor L(3)mbt was shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues...
March 6, 2018: Development
Fan Yang, Song Xu, Renwang Liu, Tao Shi, Xiongfei Li, Xuebing Li, Gang Chen, Hongyu Liu, Qinghua Zhou, Jun Chen
Introduction: Neurofibromatosis type 1 (NF1) is a common Mendelian multi-system disorder that is characterized by café-au-lait spots (CLS), axillary freckling, optic glioma and plexiform neurofibroma. Various mutations of the NF1 gene are widely accepted to be the main cause of this disease, while whether there are still certain other modifier genes that could influence the phenotypes of NF1 is our concern. Patients and Methods: One proband and his father are involved, who are characterized by plexiform neurofibroma and cutaneous neurofibroma, respectively...
2018: OncoTargets and Therapy
Niannian Li, Xiaoling Tong, Jie Zeng, Gang Meng, Fuze Sun, Hai Hu, Jiangbo Song, Cheng Lu, Fangyin Dai
Hippo signaling pathway (signaling pathway Hippo, hereinafter referred to as the Hippo pathway) was the earliest found in Drosophila (Schneck [1]), which can regulate the development of tissues and organs, even some components of the pathway were identified as tumor suppressor [2]. The pathway was more concerned in fruit flies and mice (Schneck [1]), but little attention has been given in silkworm, an important economic and lepidopteran model insect. In this manuscript, we identified major Hippo pathway related genes (Hippo, Salvador, Warts, Mats, Yorkie) in silkworm and named BmHpo, BmSav, BmWts, BmMats, BmYki...
March 1, 2018: Genomics
Shaoxin Cai, Xuefei Cheng, Yi Liu, Zhizun Lin, Wei Zeng, Changshun Yang, Lihang Liu, Ozor Anthony Chukwuebuka, Weihua Li
Blood vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as vascular endothelial growth factor(VEGF) to induce angiogenesis, thereby promoting metastasis. Here, we report that The Drosophila Eyes Absent Homologue 1 (EYA1), which is overexpressed in colorectal tumor cells, can promote colorectal tumor angiogenesis by coordinating with the hypoxia-inducible factor 1 (HIF-1α) to increase the expression of VEGF-A. Moreover, data indicated that the enhancement of HIF-1α expression by Eya1 depended on its ability to activate the phosphatidylinositol 3-kinase (PI3K) signaling pathways to increase the phosphorylation of AKT subunits...
February 26, 2018: Experimental Cell Research
Colin D Donohoe, Gábor Csordás, Andreia Correia, Marek Jindra, Corinna Klein, Bianca Habermann, Mirka Uhlirova
Interplay between apicobasal cell polarity modules and the cytoskeleton is critical for differentiation and integrity of epithelia. However, this coordination is poorly understood at the level of gene regulation by transcription factors. Here, we establish the Drosophila activating transcription factor 3 (atf3) as a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the tumor suppressors Scribble or Dlg1 induces atf3 expression via aPKC but independent of Jun-N-terminal kinase (JNK) signaling...
March 1, 2018: PLoS Genetics
Juliane Mohr, Banaja P Dash, Tina M Schnoeder, Denise Wolleschak, Carolin Herzog, Nuria Tubio Santamaria, Sönke Weinert, Sonika Godavarthy, Costanza Zanetti, Michael Naumann, Björn Hartleben, Tobias B Huber, Daniela S Krause, Thilo Kähne, Lars Bullinger, Florian H Heidel
Cell fate determinants influence self-renewal potential of hematopoietic stem cells. Scribble and Llgl1 belong to the Scribble polarity complex and reveal tumor-suppressor function in drosophila. In hematopoietic cells, genetic inactivation of Llgl1 leads to expansion of the stem cell pool and increases self-renewal capacity without conferring malignant transformation. Here we show that genetic inactivation of its putative complex partner Scribble results in functional impairment of hematopoietic stem cells (HSC) over serial transplantation and during stress...
January 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
Mariana Muzzopappa, Marco Milán
The growth of epithelial tumors is often governed by cell interactions with the surrounding stroma. Drosophila has been instrumental in identifying the relevant molecular elements mediating these interactions. Of note is the role of the TNF ligand Eiger, released from recruited blood cells, in activating the JNK tumor-promoting pathway in epithelial tumors. JNK drives the transcriptional induction of mitogenic molecules, matrix metalloproteases and systemic signals that lead to tumor growth, tissue invasiveness and malignancy...
February 16, 2018: Fly
Ofelia Tacchelly-Benites, Zhenghan Wang, Eungi Yang, Hassina Benchabane, Ai Tian, Michael P Randall, Yashi Ahmed
The aberrant activation of Wnt signal transduction initiates the development of 90% of colorectal cancers, the majority of which arise from inactivation of the tumor suppressor Adenomatous polyposis coli (APC). In the classical model for Wnt signaling, the primary role of APC is to act, together with the concentration-limiting scaffold protein Axin, in a "destruction complex" that directs the phosphorylation and consequent proteasomal degradation of the transcriptional activator β-catenin, thereby preventing signaling in the Wnt-off state...
February 2018: PLoS Genetics
Paul Hadweh, Iro Chaitoglou, Maria Joao Gravato-Nobre, Petros Ligoxygakis, George Mosialos, Eudoxia Hatzivassiliou
The human cylindromatosis tumor suppressor (HsCyld) has attracted extensive attention due to its association with the development of multiple types of cancer. HsCyld encodes a deubiquitinating enzyme (HsCYLD) with a broad range of functions that include the regulation of several cell growth, differentiation and death pathways. HsCyld is an evolutionarily conserved gene. Homologs of HsCyld have been identified in simple model organisms such as Drosophila melanogaster and Caenorhabditis elegans (C. elegans) which offer extensive possibilities for functional analyses...
2018: PloS One
Chijiang Gu, Mingyuan Zhang, Weiliang Sun, Changzheng Dong
Colorectal cancer (CRC) is a common clinical cancer, which remains incurable in most cases. MiRNAs are reported to playa part in development of various tumors. In the present study, we found that miR-324-5p was down-regulated in colorectal cancer cells while ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-Like Protein 1 (ELAVL1) showed a higher expression. MiR-324-5p transfection significantly inhibited the proliferation as well as invasion in both SW620 and SW480 cells. MiR-324-5p mimics transfection markedly decreased the expression of ELAVL1...
January 31, 2018: Oncology Research
Tanmoy Mondal, Indira Bag, Pushpavalli Sncvl, Koteswara Rao Garikapati, Utpal Bhadra, Manika Pal Bhadra
Argonaute family proteins are well conserved among all organisms. Its role in mitotic cell cycle progression and apoptotic cell elimination is poorly understood. Earlier we have established the contribution of Ago-1 in cell cycle control related to G2/M cyclin in Drosophila. Here we have extended our study in understanding the relationship of Ago-1 in regulating apoptosis during Drosophila development. Apoptosis play a critical role in controlling organ shape and size during development of multi cellular organism...
2018: PloS One
Puja Khanna, Pei Jou Chua, Belinda Shu Ee Wong, Changhong Yin, Aye Aye Thike, Wei Keat Wan, Puay Hoon Tan, Gyeong Hun Baeg
Dysregulated JAK/STAT signaling has been implicated in the molecular pathogenesis of gastric cancer. However, downstream effectors of STAT signaling that facilitate gastric carcinogenesis remain to be explored. We previously identified the Drosophila ortholog of human GRAMD1B in our genome-wide RNAi screen to identify novel components of the JAK/STAT signaling pathway in Drosophila. Here, we examined the involvement of GRAMD1B in JAK/STAT-associated gastric carcinogenesis. We found that GRAMD1B expression is positively regulated by JAK/STAT signaling and GRAMD1B inhibition decreases STAT3 levels, suggesting the existence of a positive feedback loop...
December 29, 2017: Oncotarget
Qiumin Tan, Lorenzo Brunetti, Maxime W C Rousseaux, Hsiang-Chih Lu, Ying-Wooi Wan, Jean-Pierre Revelli, Zhandong Liu, Margaret A Goodell, Huda Y Zoghbi
Capicua (CIC) regulates a transcriptional network downstream of the RAS/MAPK signaling cascade. In Drosophila , CIC is important for many developmental processes, including embryonic patterning and specification of wing veins. In humans, CIC has been implicated in neurological diseases, including spinocerebellar ataxia type 1 (SCA1) and a neurodevelopmental syndrome. Additionally, we and others have reported mutations in CIC in several cancers. However, whether CIC is a tumor suppressor remains to be formally tested...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yasuhiro Saito, Ridhdhi R Desai, Senthil K Muthuswamy
Cell polarity is a fundamental property used to generate asymmetry and structure in all cells. Cancer is associated with loss of cell and tissue structure. While observations made in model system such as Drosophila, identify polarity regulators as tumor suppressors that cause inappropriate cell division, studies in mammalian epithelia do not always support such a causative contribution. Our analysis of published cancer dataset shows that many polarity genes, including PARD6B, SCRIB, PRKCI, DLG1, DLG2, DLG5 and LLGL2, are frequently amplified in multiple cancers raising the possibility that mammalian epithelia may have evolved to use polarity proteins in multiple ways where they may have tumor promoting functions...
January 21, 2018: Biochimica et Biophysica Acta
Scott G Daniel, Atlantis D Russ, Kathryn M Guthridge, Ammad I Raina, Patricia S Estes, Linda M Parsons, Helena E Richardson, Joyce A Schroeder, Daniela C Zarnescu
Drosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP), a miRNA associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway...
December 20, 2017: Biology Open
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