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https://www.readbyqxmd.com/read/29764959/a-targeted-rnai-screen-reveals-drosophila-female-sterile-genes-that-control-the-size-of-germline-stem-cell-niche-during-development
#1
Yueh Cho, Chun-Ming Lai, Kun-Yang Lin, Hwei-Jan Hsu
Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue...
May 15, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29764501/eya4-inhibits-hepatocellular-carcinoma-growth-and-invasion-by-suppressing-nf-%C3%AE%C2%BAb-dependent-rap1-transactivation
#2
Shi-Jing Mo, Xun Hou, Xiao-Yi Hao, Jian-Peng Cai, Xin Liu, Wei Chen, Dong Chen, Xiao-Yu Yin
BACKGROUND: Our previous studies demonstrated that eyes absent homolog 4 (EYA4), a member of the eye development-related EYA family in Drosophila, is frequently methylated and silenced in hepatocellular carcinoma (HCC) specimens and associated with shorter survival. The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC. METHODS: Stable EYA4-expressing plasmid (pEYA4) transfectants of the human HCC cell lines Huh-7 and PLC/PRF/5 (PLC) were established...
April 3, 2018: Cancer communications
https://www.readbyqxmd.com/read/29749524/multifaceted-regulation-and-functions-of-yap-taz-in-tumors-review
#3
Huirong Liu, Suya Du, Tiantian Lei, Hailian Wang, Xia He, Rongsheng Tong, Yi Wang
The Hippo pathway, initially identified through screenings for mutant tumor suppressors in Drosophila, is an evolutionarily conserved signaling pathway that controls organ size by regulating cell proliferation and apoptosis. Abnormal regulation of the Hippo pathway may lead to cancer in mammals. As the major downstream effectors of the Hippo pathway, unphosphorylated Yes-associated protein (YAP) and its homolog transcriptional co-activator TAZ (also called WWTR1) (hereafter called YAP/TAZ) are translocated into the nucleus...
May 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29742619/loss-of-function-mutation-in-hippo-suppressed-enlargement-of-lysosomes-and-neurodegeneration-caused-by-dfig4-knockdown
#4
Yukie Kushimura, Yumiko Azuma, Ikuko Mizuta, Yuuka Muraoka, Akane Kyotani, Hideki Yoshida, Takahiko Tokuda, Toshiki Mizuno, Masamitsu Yamaguchi
Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy, and more than 80 CMT-causing genes have been identified to date. CMT4J is caused by a loss-of-function mutation in the Factor-Induced-Gene 4 (FIG4) gene, the product of which plays important roles in endosome-lysosome homeostasis. We hypothesized that Mammalian sterile 20-like kinase (MST) 1 and 2, tumor-suppressor genes, are candidate modifiers of CMT4J. We therefore examined the interaction between dFIG4 and Hippo (hpo), Drosophila counterparts of FIG4 and MSTs, respectively, using the Drosophila CMT4J model with the knockdown of dFIG4...
May 8, 2018: Neuroreport
https://www.readbyqxmd.com/read/29742423/cdk5-inhibition-resolves-pka-camp-independent-activation-of-creb1-signaling-in-glioma-stem-cells
#5
Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J Brat
Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29738712/drosophila-tnf-modulates-tissue-tension-in-the-embryo-to-facilitate-macrophage-invasive-migration
#6
Aparna Ratheesh, Julia Biebl, Jana Vesela, Michael Smutny, Ekaterina Papusheva, S F Gabriel Krens, Walter Kaufmann, Attila Gyoergy, Alessandra Maria Casano, Daria E Siekhaus
Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm...
May 7, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29728368/-in-vivo-expansion-of-functionally-integrated-gabaergic-interneurons-by-targeted-increase-in-neural-progenitors
#7
Rachel E Shaw, Benjamin Kottler, Zoe N Ludlow, Edgar Buhl, Dongwook Kim, Sara Morais da Silva, Alina Miedzik, Antoine Coum, James Jl Hodge, Frank Hirth, Rita Sousa-Nunes
A central hypothesis for brain evolution is that it might occur via expansion of progenitor cells and subsequent lineage-dependent formation of neural circuits. Here, we report in vivo amplification and functional integration of lineage-specific circuitry in Drosophila Levels of the cell fate determinant Prospero were attenuated in specific brain lineages within a range that expanded not only progenitors but also neuronal progeny, without tumor formation. Resulting supernumerary neural stem cells underwent normal functional transitions, progressed through the temporal patterning cascade, and generated progeny with molecular signatures matching source lineages...
May 4, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29719260/yorkie-and-jnk-control-tumorigenesis-in-drosophila-cells-with-cytokinesis-failure
#8
Stephan U Gerlach, Teresa Eichenlaub, Héctor Herranz
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. Here, we use Drosophila epithelial cells to investigate the consequences of cytokinesis failure in vivo. We report that cleavage defects trigger the activation of the JNK pathway, leading to downregulation of the inhibitor of apoptosis DIAP1 and programmed cell death...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29681543/the-pou-oct-transcription-factor-nubbin-controls-the-balance-of-intestinal-stem-cell-maintenance-and-differentiation-by-isoform-specific-regulation
#9
Xiongzhuo Tang, Yunpo Zhao, Nicolas Buchon, Ylva Engström
Drosophila POU/Oct transcription factors are required for many developmental processes, but their putative regulation of adult stem cell activity has not been investigated. Here, we show that Nubbin (Nub)/Pdm1, homologous to mammalian OCT1/POU2F1 and related to OCT4/POU5F1, is expressed in gut epithelium progenitor cells. We demonstrate that the nub-encoded protein isoforms, Nub-PB and Nub-PD, play opposite roles in the regulation of intestinal stem cell (ISC) maintenance and differentiation. Depletion of Nub-PB in progenitor cells increased ISC proliferation by derepression of escargot expression...
April 17, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29679561/drosophila-nucleostemin-3-is-required-to-maintain-larval-neuroblast-proliferation
#10
Patrick W Johnson, Chris Q Doe, Sen-Lin Lai
Stem cells must maintain proliferation during tissue development, repair and homeostasis, yet avoid tumor formation. In Drosophila, neural stem cells (neuroblasts) maintain proliferation during embryonic and larval development and terminate cell cycle during metamorphosis. An important question for understanding how tissues are generated and maintained is: what regulates stem cell proliferation versus differentiation? We performed a genetic screen which identified nucleostemin 3 (ns3) as a gene required to maintain neuroblast proliferation...
April 18, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29677182/foxo-restricts-growth-and-differentiation-of-cells-with-elevated-torc1-activity-under-nutrient-restriction
#11
Katarzyna Nowak, Avantika Gupta, Hugo Stocker
TORC1, a central regulator of cell survival, growth, and metabolism, is activated in a variety of cancers. Loss of the tumor suppressors PTEN and Tsc1/2 results in hyperactivation of TORC1. Tumors caused by the loss of PTEN, but not Tsc1/2, are often malignant and have been shown to be insensitive to nutrient restriction (NR). In Drosophila, loss of PTEN or Tsc1 results in hypertrophic overgrowth of epithelial tissues under normal nutritional conditions, and an enhanced TORC1-dependent hyperplastic overgrowth of PTEN mutant tissue under NR...
April 20, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29661224/notch-signals-modulate-lgl-mediated-tumorigenesis-by-the-activation-of-jnk-signaling
#12
Maimuna Sali Paul, Ankita Singh, Debdeep Dutta, Mousumi Mutsuddi, Ashim Mukherjee
OBJECTIVES: Oncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to induce neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs large to induce neoplastic overgrowth and invasion. Our study aims at assessing the cooperation of activated Notch with loss of function of lgl in tumor overgrowth, and the mode of JNK signaling activation in this context...
April 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29617376/brain-tumor-promotes-axon-growth-across-the-midline-through-interactions-with-the-microtubule-stabilizing-protein-apc2
#13
Elise Arbeille, Greg J Bashaw
Commissural axons must cross the midline to establish reciprocal connections between the two sides of the body. This process is highly conserved between invertebrates and vertebrates and depends on guidance cues and their receptors to instruct axon trajectories. The DCC family receptor Frazzled (Fra) signals chemoattraction and promotes midline crossing in response to its ligand Netrin. However, in Netrin or fra mutants, the loss of crossing is incomplete, suggesting the existence of additional pathways. Here, we identify Brain Tumor (Brat), a tripartite motif protein, as a new regulator of midline crossing in the Drosophila CNS...
April 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29615570/drosophila-as-a-model-to-study-the-link-between-metabolism-and-cancer
#14
REVIEW
Héctor Herranz, Stephen M Cohen
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. Drosophila melanogaster is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation. In this review, we discuss the use of Drosophila as model to study how changes in cellular metabolism, as well as metabolic disease, contribute to cancer...
December 1, 2017: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29615557/wingless-wnt-signaling-in-intestinal-development-homeostasis-regeneration-and-tumorigenesis-a-drosophila-perspective
#15
REVIEW
Ai Tian, Hassina Benchabane, Yashi Ahmed
In mammals, the Wnt/β-catenin signal transduction pathway regulates intestinal stem cell maintenance and proliferation, whereas Wnt pathway hyperactivation, resulting primarily from the inactivation of the tumor suppressor Adenomatous polyposis coli (APC), triggers the development of the vast majority of colorectal cancers. The Drosophila adult gut has recently emerged as a powerful model to elucidate the mechanisms by which Wingless/Wnt signaling regulates intestinal development, homeostasis, regeneration, and tumorigenesis...
March 28, 2018: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29602952/regulation-of-the-hippo-pathway-in-cancer-biology
#16
REVIEW
Sungho Moon, So Yeon Park, Hyun Woo Park
The Hippo tumor suppressor pathway, which is well conserved from Drosophila to humans, has emerged as the master regulator of organ size, as well as major cellular properties, such as cell proliferation, survival, stemness, and tissue homeostasis. The biological significance and deregulation of the Hippo pathway in tumorigenesis have received a surge of interest in the past decade. In the current review, we present the major discoveries that made substantial contributions to our understanding of the Hippo pathway and discuss how Hippo pathway components contribute to cellular signaling, physiology, and their potential implications in anticancer therapeutics...
March 30, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29592892/gene-dosage-effect-of-cux1-in-a-murine-model-disrupts-hsc-homeostasis-and-controls-the-severity-and-mortality-of-mds
#17
Ningfei An, Saira Khan, Molly K Imgruet, Sandeep K Gurbuxani, Stephanie N Konecki, Michael R Burgess, Megan E McNerney
Monosomy 7 (-7) and del(7q) are high-risk cytogenetic abnormalities common in myeloid malignancies. We previously reported that CUX1 , a homeodomain-containing transcription factor encoded on 7q22, is frequently inactivated in myeloid neoplasms, and CUX1 myeloid tumor suppressor activity is conserved from humans to Drosophila CUX1 inactivating mutations are recurrent in clonal hematopoiesis of indeterminate potential (CHIP) as well as myeloid malignancies, in which they independently carry a poor prognosis...
March 28, 2018: Blood
https://www.readbyqxmd.com/read/29580384/the-asymmetrically-segregating-lncrna-cherub-is-required-for-transforming-stem-cells-into-malignant-cells
#18
Lisa Landskron, Victoria Steinmann, Francois Bonnay, Thomas R Burkard, Jonas Steinmann, Ilka Reichardt, Heike Harzer, Anne-Sophie Laurenson, Heinrich Reichert, Jürgen A Knoblich
Tumor cells display features that are not found in healthy cells. How they become immortal and how their specific features can be exploited to combat tumorigenesis are key questions in tumor biology. Here we describe the long non-coding RNA cherub that is critically required for the development of brain tumors in Drosophila but is dispensable for normal development. In mitotic Drosophila neural stem cells, cherub localizes to the cell periphery and segregates into the differentiating daughter cell. During tumorigenesis, de-differentiation of cherub-high cells leads to the formation of tumorigenic stem cells that accumulate abnormally high cherub levels...
March 27, 2018: ELife
https://www.readbyqxmd.com/read/29578365/the-capicua-tumor-suppressor-a-gatekeeper-of-ras-signaling-in-development-and-cancer
#19
Lucía Simón-Carrasco, Gerardo Jiménez, Mariano Barbacid, Matthias Drosten
The transcriptional repressor Capicua (CIC) has emerged as an important rheostat of cell growth regulated by RAS/MAPK signaling. Cic was originally discovered in Drosophila, where it was shown to be inactivated by MAPK signaling downstream of the RTKs Torso and EGFR, which results in signal-dependent responses that are required for normal cell fate specification, proliferation and survival of developing and adult tissues. CIC is highly conserved in mammals, where it is also negatively regulated by MAPK signaling...
March 26, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29568120/role-of-hippo-signaling-in-regulating-immunity
#20
REVIEW
Lixin Hong, Xun Li, Dawang Zhou, Jing Geng, Lanfen Chen
The Hippo signaling pathway has been established as a key regulator of organ size control, tumor suppression, and tissue regeneration in multiple organisms. Recently, emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals. In particular, patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases, the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity...
March 22, 2018: Cellular & Molecular Immunology
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