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Molecular & Cellular Oncology

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https://www.readbyqxmd.com/read/30263950/dna-repair-synthesis-and-histone-deposition-partner-during-homologous-recombination
#1
Amira Elbakry, Szilvia Juhász, Arthur Mathes, Markus Löbrich
Chromatin remodeling is critical for the regulation of the DNA damage response. We highlight findings from our recent study showing that the deposition of the histone variant H3.3 by the alpha-thalassemia mental retardation X-linked protein (ATRX) and the death domain associated protein (DAXX) chromatin remodeling complex regulates DNA repair synthesis during homologous recombination.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263949/local-unwinding-of-double-strand-dna-ends-by-the-mrx-complex-promotes-exo1-processing-activity
#2
Elisa Gobbini, Jacopo Vertemara, Maria Pia Longhese
Homologous recombination is initiated by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs), which involves different nucleases including the Mre11-Rad50-Xrs2 (MRX) complex and the Exonuclease 1 (Exo1). The characterization of a novel mutation in Mre11 causing accelerated DSB resection has allowed to show that MRX facilitates DNA end processing by Exo1 through local unwinding of double-stranded DNA ends.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263948/cdk6-at-the-interface-of-rb-and-p53
#3
Sofie Nebenfuehr, Florian Bellutti, Veronika Sexl
In cancer the activity of cyclin-dependent kinase 4-(CDK4) and cyclin-dependent kinase 6 (CDK6)-cyclin complexes are frequently altered with enhanced CDK6 expression found in hematopoietic malignancies. Our latest findings show a so far unknown role of Cdk6 during oncogene-induced stress and transformation. Therein Cdk6 antagonizes p53 responses and subsequently shapes the critical decision between survival and apoptosis in pre-leukemic cells.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263947/dynamic-erk-signaling-regulation-in-intestinal-tumorigenesis
#4
Yu Muta, Michiyuki Matsuda, Masamichi Imajo
Extracellular signal-regulated kinase (ERK) plays a critical role in tissue homeostasis and tumorigenesis. By utilizing live imaging approaches, we recently uncovered ERK activity dynamics in the intestinal epithelium. Notably, we showed that ERK activity dynamics are defined by composite regulation from two distinct upstream receptors, and alteration of their functional balance underlies tumor cell-specific traits. Here, we discuss these findings.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263946/give-me-a-sine-how-selective-inhibitors-of-nuclear-export-modulate-autophagy-and-aging
#5
A V Kumar, T G Thakurta, M J Silvestrini, J R Johnson, R A Reenan, L R Lapierre
Autophagy is a cellular recycling process leading to lysosomal degradation of damaged macromolecules, which can protect cells against aging. The transcription factor EB (TFEB), a major transcriptional regulator of genes involved in autophagy and lysosomal function, is emerging as an attractive target for pharmacological modulation. Recently, we demonstrated that inhibiting the function of nuclear export protein exportin 1 (XPO1 or CRM1) with RNAi or with selective inhibitors of nuclear export (SINE) results in the nuclear enrichment of TFEB and enhancement of autophagy in model organisms and human cells...
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263945/ubiquitination-and-adaptive-responses-to-braf-inhibitors-in-melanoma
#6
Azad Saei, Pieter Johan Adam Eichhorn
Response to targeted therapies is limited by the activation or inhibition of feedback loops. Here we report the ubiquitin specific peptidase 28/F-box WD repeat-containing protein 7 (USP28/FBW7) complex functions as a negative regulator of mitogen-activated protein kinase (MAPK) pathway by targeting v-raf murine sarcoma viral oncogene homolog B (BRAF) for degradation, a process which is lost in a large proportion of BRAF mutant melanoma patients, resulting in resistance to BRAF inhibitor therapies.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263944/a-balancing-act-mtor-integrates-nutrient-signals-to-regulate-redox-dependent-growth-and-survival-through-sod1
#7
Chi Kwan Tsang, X F Steven Zheng
Maintaining cellular redox is critical for growth, metabolism and survival in response to changing environments. How nutrients regulate this process is a long-standing fundamental question in cell biology. Our recent study revealed a conserved mechanism by which eukaryotes, particularly cancer cells, couple nutrient signaling to dynamically regulate redox homeostasis. Abbreviations: ATP: adenosine triphosphate; Ala: alanine; C6 H12 O6 : glucose; OH- : hydroxyl radical; Glu: glutamate; mRNA: messenger RNA; mTOR: mechanistic/mammalian target of rapamycin; OXYPHOS: oxidative phosphorylation; Ser: serine; ROS: reactive oxygen species; O2 - : superoxide; SOD1: superoxide dismutase 1; Thr: threonine...
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263943/tumor-evolution-multiple-induction-mechanisms-for-cell-competition
#8
Abhijit Kale, Nicholas E Baker
Tumor cells often differ genetically from normal cells and from one another. Competitive interactions can occur between genetically-distinct cells, and recent studies highlight multiple examples where cell competition initiates using distinct pathways.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263942/single-cell-mass-cytometry-and-machine-learning-predict-relapse-in-childhood-leukemia
#9
Jolanda Sarno, Kara L Davis
Improved insight into cancer cell populations responsible for treatment failure will lead to better outcomes for patients. We herein highlight a single-cell study of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) at diagnosis that revealed hidden developmentally dependent cell signaling states uniquely associated with relapse.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263941/dual-mechanism-of-dicer-downregulation-facilitates-cancer-metastasis
#10
Hui-Huang Lai, Pai-Sheng Chen
Although downregulation of DICER - a critical enzyme in microRNA (miRNA) maturation - reportedly promotes cancer metastasis, understanding of its upstream regulators remains limited. Our recent study demonstrated a noncanonical oncogenic effect of hypoxia-inducible factor-1α (HIF-1α), which directly binds with DICER to promote PARKIN-mediated autophagic-lysosomal proteolysis and consequently suppresses miRNA biogenesis, facilitating metastasis.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263940/novel-insights-into-the-epigenetics-of-diffuse-glioma
#11
Carla Danussi, Jason T Huse
Loss-of-function mutations of the chromatin regulator ATRX (α-thalassemia mental retardation X-linked) occur frequently in diffuse gliomas, but the molecular mechanisms by which ATRX inactivation promotes oncogenesis remain unclear. We recently reported that Atrx deficiency drives glioma-relevant phenotypes, such as increased motility and astrocytic differentiation profiles, by directly modulating epigenomic lanscapes in glioma cells of origin. Our work has significant implications on the role of epigenetic regulator dysfunction in the oncogenic process...
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263939/ccpg1-an-unconventional-cargo-receptor-for-er-phagy-maintains-pancreatic-acinar-cell-health
#12
Matthew D Smith, Simon Wilkinson
ER stress-mediated induction of a new vertebrate-specific autophagy cargo receptor, CCPG1 (cell-cycle progression gene 1), drives degradation of endoplasmic reticulum. CCPG1 acts via ATG8-family interaction and, non-canonically, via discrete interactions with FIP200. CCPG1 ameliorates ER stress in the exocrine pancreas. This has potential implications for inflammation and cancer, discussed here.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263938/leptin-revisited-the-role-of-leptin-in-starvation
#13
Rachel J Perry
Starvation causes reductions in plasma leptin concentrations, but the physiologic impact of this observation had not been documented in the starved state. Here we discuss our recent work demonstrating that hypoleptinemia activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing white adipose tissue (WAT) lipolysis and mediating a shift from glucose to fat metabolism to maintain euglycemia in fasted rats.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263937/targeting-mutagenesis-in-b-cells-phosphorylation-goes-beyond-aid-association
#14
Yunxiang Mu, Kevin M McBride
The mutations induced by activation-induced cytidine deaminase (AID) trigger antibody diversification but can cause genome instability. We find that AID phosphorylation is an important determinant of "off-target" mutagenesis and identify a drug that increases this activity. These studies demonstrate how dysregulating AID phosphorylation can promote oncogenesis.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263936/cdk4-a-new-metabolic-sensor-that-antagonizes-ampk
#15
L Fajas, I C Lopez-Mejia
Cyclin-dependent kinase 4 (CDK4) is a positive regulator of cell cycle progression, however, there is growing evidence demonstrating that its function exceeds the control of cell division. Here we show that CDK4 is an important regulator of cellular substrate utilization through direct inhibition of the metabolic regulator AMPK (AMP-activated protein kinase).
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263935/regulation-of-protein-metabolism-in-cancer
#16
Cecil Han, Xiongbin Lu, Deepak Nagrath
Our recent studies determined molecular interactions between genes in the ubiquitin-proteasome pathways and cancer cell metabolism. Ubiquitin-specific peptidase 13 (USP13) specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase that drive ovarian cancer metabolism. These findings may lead to the development of USP13 inhibitors and new-targeted therapies in ovarian cancers.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263934/protein-kinase-c-%C3%AE-a-versatile-oncogene-in-the-lung
#17
Alan P Fields, Syed A Ali, Verline Justilien, Nicole R Murray
We have recently demonstrated that protein kinase C ι (PKC ι ) promotes a stem-like, tumor-initiating cell phenotype in KRAS -driven lung adenocarcinoma by activating a novel ELF3-NOTCH3 signaling axis.1 Combined PKC ι and NOTCH inhibition was identified as a novel strategy for the treatment of KRAS -driven lung adenocarcinoma.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263933/the-role-of-polycomb-repressive-complex-2-in-early-t-cell-precursor-acute-lymphoblastic-leukemia
#18
Kathrin M Bernt, Tobias Neff
Genetic lesions affecting polycomb repressive complex 2 (PRC2) have been found in more than 40% of pediatric cases of early T-cell precursor acute lymphoblastic leukemia. The functional role of these PRC2 alterations has been obscure. Our recent data suggest that compromise of PRC2 blocks differentiation and accentuates growth and survival signaling.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263932/mitochondrial-and-lipid-droplet-dynamics-regulate-intra-and-intercellular-fatty-acid-trafficking
#19
Sarah Cohen, Angelika S Rambold, Jennifer Lippincott-Schwartz
Imaging of fatty acid (FA) trafficking revealed that FAs stored in lipid droplets were delivered to mitochondria when the cells were starved. This delivery required cytoplasmic lipases and mitochondrial fusion activity, whereas lipid droplets were replenished with FAs supplied by autophagy. These findings have important implications for cancer.
2018: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/30263931/atg12-atg3-coordinates-basal-autophagy-endolysosomal-trafficking-and-exosome-release
#20
Lyndsay Murrow, Jayanta Debnath
We recently identified an interaction between Atg12-Atg3, a complex between 2 core autophagy regulators, and the ESCRT-associated protein Pdcd6ip (programmed cell death 6 interacting protein, commonly known as Alix), which coordinately regulates basal autophagy, late endosome-to-lysosome trafficking, and exosome release. Because these processes all serve fundamental roles in cancer progression and therapy, Atg12-Atg3 may be an attractive anticancer target.
2018: Molecular & Cellular Oncology
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