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https://www.readbyqxmd.com/read/28212585/atm-mapk7-crosstalk-in-cancer
#1
EDITORIAL
José Yélamos
News on: Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice by Granados-Jaén, et al. Oncotarget. 2016; 7(46):74435-74447. doi: 10.18632/oncotarget.12908.
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209993/suppression-of-tak1-pathway-by-shear-stress-counteracts-the-inflammatory-endothelial-cell-phenotype-induced-by-oxidative-stress-and-tgf-%C3%AE-1
#2
Ee Soo Lee, Llorenç Solé Boldo, Bernadette O Fernandez, Martin Feelisch, Martin C Harmsen
Endothelial dysfunction is characterised by aberrant redox signalling and an inflammatory phenotype. Shear stress antagonises endothelial dysfunction by increasing nitric oxide formation, activating anti-inflammatory pathways and suppressing inflammatory pathways. The TAK1 (MAP3K7) is a key mediator of inflammation and non-canonical TGF-β signalling. While the individual roles of TAK1, ERK5 (MAPK7) and TGF-β pathways in endothelial cell regulation are well characterised, an integrative understanding of the orchestration of these pathways and their crosstalk with the redox system under shear stress is lacking...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153789/mek5-erk5-signaling-in-cancer-implications-for-targeted-therapy
#3
Van T Hoang, Thomas J Yan, Jane E Cavanaugh, Patrick T Flaherty, Barbara S Beckman, Matthew E Burow
Mitogen-activated protein kinases (MAPKs) regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis. While conventional MAPK constituents have well-defined roles in oncogenesis, the MEK5 pathway has only recently emerged in cancer research. In this review, we consider the MEK5 signaling cascade, focusing specifically on its involvement in drug resistance and regulation of aggressive cancer phenotypes. Moreover, we explore the role of MEK5/ERK5 in tumorigenesis and metastatic progression, discussing the discrepancies in preclinical studies and assessing its viability as a therapeutic target for anti-cancer agents...
January 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28153028/il-1%C3%AE-impairs-retrograde-flow-of-bdnf-signaling-by-attenuating-endosome-trafficking
#4
Anthony J Carlos, Liqi Tong, G Aleph Prieto, Carl W Cotman
BACKGROUND: Pro-inflammatory cytokines accumulate in the brain with age and Alzheimer's disease and can impair neuron health and cognitive function. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that supports neuron health, function, and synaptic plasticity. The pro-inflammatory cytokine interleukin-1β (IL-1β) impairs BDNF signaling but whether it affects BDNF signaling endosome trafficking has not been studied. METHODS: This study uses an in vitro approach in primary hippocampal neurons to evaluate the effect of IL-1β on BDNF signaling endosome trafficking...
February 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28131816/traf1-is-critical-for-dmba-solar-uv-induced-skin-carcinogenesis
#5
Hiroyuki Yamamoto, Joohyun Ryu, Eli Min, Naomi Oi, Ruihua Bai, Tatyana A Zykova, Dong Hoon Yu, Kenji Moriyama, Ann M Bode, Zigang Dong
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF protein family, which regulates the canonical and non-canonical NF-κB signaling cascades. Although aberrant TRAF1 expression in tumors has been reported, the role of TRAF1 remains elusive. Here, we report that TRAF1 is required for solar UV-induced skin carcinogenesis. Immunohistochemical analysis revealed that TRAF1 expression is up-regulated in human actinic keratosis (AK) and squamous cell carcinoma (SCC). In vivo studies indicated that TRAF1 expression levels in mouse skin are induced by short-term solar UV irradiation and a long-term skin carcinogenesis study demonstrated that deletion of TRAF1 in mice results in a significant inhibition of skin tumor formation...
January 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28130552/melatonin-micronutrients-osteopenia-treatment-study-mots-a-translational-study-assessing-melatonin-strontium-citrate-vitamin-d3-and-vitamin-k2-mk7-on-bone-density-bone-marker-turnover-and-health-related-quality-of-life-in-postmenopausal-osteopenic-women-following
#6
Sifat Maria, Mark H Swanson, Larry T Enderby, Frank D'Amico, Brianna Enderby, Rebekah M Samsonraj, Amel Dudakovic, Andre J van Wijnen, Paula A Witt-Enderby
This one-year double blind randomized control trial assessed the effects of nightly melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7; MSDK) on bone mineral density (BMD) and quality of life (QOL) in postmenopausal osteopenic women (ages 49-75). Compared to placebo, MSDK treatment increased BMD in lumbar spine (4.3%) and left femoral neck (2.2%), with an upward trend for total left hip (p=0.069). MSDK increased serum P1NP levels and reduced bone turnover (CTx:P1NP). Psychometric analyses indicated that mood and sleep quality improved for the MSDK group...
January 26, 2017: Aging
https://www.readbyqxmd.com/read/28079882/stability-of-the-cancer-target-ddias-is-regulated-by-the-chip-hsp70-pathway-in-lung-cancer-cells
#7
Kyoung-Jae Won, Joo-Young Im, Bo-Kyung Kim, Hyun Seung Ban, Young-Jin Jung, Kyeong Eun Jung, Misun Won
DNA damage-induced apoptosis suppressor (DDIAS) rescues lung cancer cells from apoptosis in response to DNA damage. DDIAS is transcriptionally activated by NFATc1 and EGF-mediated ERK5/MEF2B, leading to cisplatin resistance and cell invasion. Therefore, DDIAS is suggested as a therapeutic target for lung cancer. Here, we report that DDIAS stability is regulated by E3 U-box ubiquitin ligase carboxyl terminus of HSP70-interacting protein (CHIP)-mediated proteasomal degradation. We first isolated CHIP as an interacting partner of DDIAS by yeast two-hybrid screening...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28029186/adipokine-chemerin-bridges-metabolic-dyslipidemia-and-alveolar-bone-loss-in-mice
#8
Erivan S Ramos-Junior, Gisele A Leite, Cecilia C Carmo-Silva, Thaise M Taira, Karla B Neves, David F Colón, Lea Ab da Silva, Sergio L Salvador, Rita C Tostes, Fernando Q Cunha, Sandra Y Fukada
Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine-like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type-2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27982724/the-proteasome-inhibitor-bortezomib-inhibits-inflammatory-response-of-periodontal-ligament-cells-and-ameliorates-experimental-periodontitis-in-rats
#9
Lin Jiang, Jinlin Song, Xiaolei Hu, Hongmei Zhang, Enyi Huang, Yan Zhang, Feng Deng, Xiaomian Wu
BACKGROUND: Periodontitis is a chronic inflammatory disease initiated by bacteria and their virulence factors. Bortezomib (BTZ) is the first proteasome inhibitor for clinical treatment of malignancies. Its anti-cancer activity is accompanied by an anti-inflammatory effect. However, there are few reports about its anti-inflammatory effect and underlying mechanism in periodontal disease, especially on human periodontal ligament cells (hPDLCs), which are considered as a promising cell-based therapy for treating periodontitis...
December 16, 2016: Journal of Periodontology
https://www.readbyqxmd.com/read/27976059/5-7-dihydroxyflavone-analogues-may-regulate-lipopolysaccharide-induced-inflammatory-responses-by-suppressing-i%C3%AE%C2%BAb%C3%AE-linked-akt-and-erk5-phosphorylation-in-raw-264-7-macrophages
#10
A Nishina, M Ukiya, M Fukatsu, M Koketsu, M Ninomiya, D Sato, H Kimura
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#11
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for acute myeloid leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27878304/upregulation-of-mek5-by-stat3-promotes-breast-cancer-cell-invasion-and-metastasis
#12
Fang Liu, Hao Zhang, Hui Song
Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important role in promoting cell proliferation and tumorigenesis. The aberrant expression of MEK5 has been reported in various malignant diseases including cancers of breast, prostate, lung, colorectal and brain. However, the function and regulation of MEK5 signaling pathway are ambiguous and remain elusive with respect to its oncogenic roles in various cancers, especially in the regulation of the initiation and progression of cancer invasion and metastasis...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27851987/evaluation-of-inflammation-related-signaling-events-covering-phosphorylation-and-nuclear-translocation-of-proteins-based-on-mass-spectrometry-data
#13
Andrea Bileck, Rupert L Mayer, Dominique Kreutz, Tamara Weiss, Sabine Taschner-Mandl, Samuel M Meier, Astrid Slany, Christopher Gerner
: Peripheral blood mononuclear cells are important players in immune regulation relying on a complex network of signaling pathways. In this study, we evaluated the power of label-free quantitative shotgun proteomics regarding the comprehensive characterization of signaling pathways in such primary cells by studying regulation of protein abundance, post-translational modifications and nuclear translocation events. The effects of inflammatory stimulation and the treatment of stimulated cells with dexamethasone were investigated...
January 30, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/27836247/implication-of-vhl-erk5-and-hif-1alpha-in-clear-cell-renal-cell-carcinoma-molecular-basis
#14
Leticia Serrano-Oviedo, José M Giménez-Bachs, Syongh Y Nam-Cha, Francisco J Cimas, Jesús García-Cano, Ricardo Sánchez-Prieto, Antonio S Salinas-Sánchez
OBJECTIVES: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. MATERIAL AND METHODS: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables...
November 8, 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27821723/c1q-tnf-related-protein-9-promotes-cardiac-hypertrophy-and-failure
#15
Mahesh Appari, Astrid Breitbart, Florian Brandes, Malgorzata Szaroszyk, Natali Froese, Mortimer Korf-Klingebiel, Mona Malek Mohammadi, Andrea Grund, Gesine M Scharf, Honghui Wang, Carolin Zwadlo, Daniela Fraccarollo, Ulrike Schrameck, Mona Nemer, William Wong, Hugo A Katus, Kai C Wollert, Oliver J Müller, Johann Bauersachs, Joerg Heineke
RATIONALE: Myocardial endothelial cells promote cardiomyocyte hypertrophy, possibly through the release of growth factors. The identity of these factors, however, remains largely unknown, and we hypothesized here that the secreted C1q-TNF-related protein-9 (CTRP9) might act as endothelial derived protein to modulate heart remodeling in response to pressure overload. OBJECTIVE: To examine the source of cardiac CTRP9 and its function during pressure overload. METHODS AND RESULTS: CTRP9 was mainly derived from myocardial capillary endothelial cells...
November 7, 2016: Circulation Research
https://www.readbyqxmd.com/read/27806338/mir-143-suppresses-the-epithelial-mesenchymal-transition-of-spinal-glioblastoma-through-down-regulation-of-erk5
#16
Yi Yan, Jing Wu, Mingjun Wu, Yongzhi Xia, Wenyuan Tang, Zhengbu Liao
The spinal glioblastoma (GBM) represents the one of most common tumors in humans. However, the biological processes and molecular mechanisms of spinal GBM are still unclear. It is known that miR-143 participates in the development of various tumor progressions. The present study was to evaluate the level of miR-143 in spinal GBM tissues and cells. We further investigated that the molecular mechanisms of miR-143 in U87 and U251 cell lines. Here, our data showed that the expression levels of miR-143 were significantly reduced in spinal GBM tissues and cell lines...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27793024/absence-of-erk5-mapk7-delays-tumorigenesis-in-atm-mice
#17
Alba Granados-Jaén, Maria Angulo-Ibáñez, Xavier Rovira-Clavé, Celina Paola Vasquez Gamez, Francesc X Soriano, Manuel Reina, Enric Espel
Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#18
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27748139/nuclear-erk5-inhibits-progression-of-leukemic-monocytes-to-macrophages-by-regulating-the-transcription-factor-pu-1-and-heat-shock-protein-hsp70
#19
Ruifang Zheng, George P Studzinski
Differentiation therapy can supplement the therapy of APL, but other subtypes of AML are treated principally with cytotoxic agents, with few lasting remissions. While the induction of monocyte followed by macrophage differentiation by vitamin D derivatives (VDDs) is dramatic in cultured AML cells of all subtypes, attempts to translate this to the clinic have not been effective. Thus, better understanding of the mechanisms underlying VDD-induced differentiation may improve this approach. The key events in this form of differentiation include increased expression of CD11b, and the transcription factor PU...
October 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27742373/scutellarin-attenuates-vasospasm-through-the-erk5-klf2-enos-pathway-after-subarachnoid-hemorrhage-in-rats
#20
Qiang Li, Yujie Chen, Xuan Zhang, Shilun Zuo, Hongfei Ge, Yanyan Chen, Xin Liu, John H Zhang, Huaizhen Ruan, Hua Feng
Angiographic vasospasm, especially in the early phases (<72h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague-Dawley rats. Then, the underlying mechanism of the anti-vasospasm effect of SCU was investigated using a modified Garcia scale, India ink angiography, cross-sectional area analysis, immunohistochemistry staining and western blot...
December 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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