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https://www.readbyqxmd.com/read/29932870/er%C3%AE-36-gene-silencing-promotes-tau-protein-phosphorylation-inhibits-cell-proliferation-and-induces-apoptosis-in-human-neuroblastoma-sh-sy5y-cells
#1
Hong-Bin Wang, Tao Li, Dong-Zhou Ma, Hua Zhi
Neuroblastoma is the most common cancer in infants and the third most common cancer in children after leukemia and brain cancer. The purpose of our study was to investigate the effects of estrogen receptor (ER)-α36 gene silencing on tau protein phosphorylation, cell proliferation, and cell apoptosis in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with estrogen or left untreated, to investigate the effects of estrogen stimulation on ERα36 and the ERK/protein B kinase (AKT) signaling pathway...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29925043/molecular-characterization-and-putative-pathogenic-pathways-of-tuberous-sclerosis-complex-associated-renal-cell-carcinoma
#2
Jeong Hwan Park, Cheol Lee, Mee Soo Chang, Kwangsoo Kim, Seongmin Choi, Hyunjung Lee, Hyun-Seob Lee, Kyung Chul Moon
Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...
June 17, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29914877/antagonizing-set-augments-the-effects-of-radiotherapy-in-hepatocellular-carcinoma-through-reactivating-pp2a-mediated-akt-downregulation
#3
Chao-Yuan Huang, Man-Hsin Hung, Chi-Ting Shih, Feng-Shu Hsieh, Chiung-Wen Kuo, Ming-Hsien Tsai, Shih-Shin Chang, Yung-Jen Hsiao, Li-Ju Chen, Tzu-I Chao, Kuen-Feng Chen
Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiotherapy (RT)-mediated anti-cancer effects has not yet been explored. Here, we investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assay, we found that RT-induced proliferative inhibition was critically associated with SET expression. Next, we tested a novel SET antagonist, EMQA, in combination with RT...
June 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29844385/cd24-regulates-sorafenib-resistance-via-activating-autophagy-in-hepatocellular-carcinoma
#4
Shuai Lu, Yao Yao, Guolong Xu, Chao Zhou, Yuan Zhang, Jie Sun, Runqiu Jiang, Qing Shao, Yun Chen
Hepatocellular carcinoma is one of most common solid cancers worldwide. Sorafenib is indicated as a treatment for advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib has been severely compromised by the development of drug resistance, and the precise mechanisms of drug resistance remain largely unknown. Here we found that a cell surface molecule, CD24, is overexpressed in tumor tissues and sorafenib-resistant hepatocellular carcinoma cell lines. Moreover, there is a positive correlation between CD24 expression levels and sorafenib resistance...
May 29, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29792865/aspirin-restores-abt-737-mediated-apoptosis-in-human-renal-carcinoma-cells
#5
Yen-Chuan Ou, Jian-Ri Li, Jiaan-Der Wang, Wen-Ying Chen, Yu-Hsiang Kuan, Ching-Ping Yang, Su-Lan Liao, Hsi-Chi Lu, Chun-Jung Chen
Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29743597/mastl-overexpression-promotes-chromosome-instability-and-metastasis-in-breast-cancer
#6
Samuel Rogers, Rachael A McCloy, Benjamin L Parker, David Gallego-Ortega, Andrew M K Law, Venessa T Chin, James R W Conway, Dirk Fey, Ewan K A Millar, Sandra O'Toole, Niantao Deng, Alexander Swarbrick, Paul D Chastain, Anthony J Cesare, Paul Timpson, C Elizabeth Caldon, David R Croucher, David E James, D Neil Watkins, Andrew Burgess
MASTL kinase is essential for correct progression through mitosis, with loss of MASTL causing chromosome segregation errors, mitotic collapse and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian and lung cancer. Global phosphoproteomic analysis of immortalised breast MCF10A cells engineered to overexpressed MASTL revealed disruption to desmosomes, actin cytoskeleton, PI3K/AKT/mTOR and p38 stress kinase signalling pathways...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29723508/inhibition-of-pp2a-by-hesperetin-contributes-to-akt-and-erk1-2-activation-in-primary-cortical-neurons
#7
David Vauzour, Simone Corsini, Michael Müller, Jeremy P E Spencer
Flavonoids and their metabolites are well reported to modulate the activation/phosphorylation of various cellular kinases, such as ERK1/2 and JNK, although the mechanism by which they do so is unclear. In this study, we investigated the impact of flavanones on the activation of PI3K/Akt and ERK1/2 and determine whether this is mediated, in part, by the inhibition of phosphatases. Primary cortical neurons were exposed to physiological concentrations of hesperetin and the phosphorylation status of the kinases PI3K/Akt and ERK1/2 and the phosphatases PP2A and PTEN were assessed by immunoblotting after 30 min...
April 30, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29704550/tau-hyperphosphorylation-and-p-creb-reduction-are-involved-in-acrylamide-induced-spatial-memory-impairment-suppression-by-curcumin
#8
Dandan Yan, Jianling Yao, Ying Liu, Xing Zhang, Yiqi Wang, Xiaoyi Chen, Liegang Liu, Nian Shi, Hong Yan
Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin...
July 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29703716/cip2a-and-setbp1-mediated-pp2a-inhibition-reveals-akt-s473-phosphorylation-to-be-a-new-biomarker-in-aml
#9
Claire M Lucas, Laura J Scott, Natasha Carmell, Alison K Holcroft, Robert K Hills, Alan K Burnett, Richard E Clark
No abstract text is available yet for this article.
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29623928/effect-of-tibolone-pretreatment-on-kinases-and-phosphatases-that-regulate-the-expression-and-phosphorylation-of-tau-in-the-hippocampus-of-rats-exposed-to-ozone
#10
Rodolfo Pinto-Almazan, Julia J Segura-Uribe, Marvin A Soriano-Ursúa, Eunice D Farfán-García, Juan M Gallardo, Christian Guerra-Araiza
Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3 ) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29530069/inhibition-of-creb-binding-protein-beta-catenin-signaling-down-regulates-cd133-expression-and-activates-pp2a-pten-signaling-in-tumor-initiating-liver-cancer-cells
#11
Yuanyuan Tang, Joshua Berlind, Nirmala Mavila
BACKGROUND: The WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood...
March 12, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29511968/amphetamine-neurotoxicity-in-pc12-cells-through-the-pp2a-akt-gsk3%C3%AE-pathway
#12
Wenji He, Xinyu Yan, Sanqiang Pan
Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/ glycogen synthase kinase 3 beta (AKT/GSK3β) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3β phosphorylation levels and increased total GSK-3β levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels...
March 6, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29500169/antiphospholipid-antibodies-induce-thrombosis-by-pp2a-activation-via-apoer2-dab2-shc1-complex-formation-in-endothelium
#13
Anastasia Sacharidou, Ken L Chambliss, Victoria Ulrich, Jane E Salmon, Yu-Min Shen, Joachim Herz, David Y Hui, Lance S Terada, Philip W Shaul, Chieko Mineo
In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of β2 glycoprotein I promotes thrombosis, and preclinical studies indicate that this is due to endothelial nitric oxide synthase (eNOS) antagonism via apolipoprotein E receptor 2 (apoER2)-dependent processes. How apoER2 molecularly links these events is unknown. Here, we show that, in endothelial cells, the apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of the heterotrimeric protein phosphatase 2A (PP2A)...
May 10, 2018: Blood
https://www.readbyqxmd.com/read/29470962/indomethacin-induced-glioma-apoptosis-involving-ceramide-signals
#14
Cheng-Yi Chang, Jian-Ri Li, Chih-Cheng Wu, Jiaan-Der Wang, Ching-Ping Yang, Wen-Ying Chen, Wen-Yi Wang, Chun-Jung Chen
Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly implicated in the prevention and treatment of cancers apart from their known inhibitory effects on eicosanoid production. One of the NSAIDs, indomethacin, in particular shows promising antineoplastic outcome against glioma. To extend such finding, we here studied in human H4 and U87 glioma cells the possible involvement of the ceramide/protein phosphatase 2 A (PP2A)/Akt axis in the indomethacin-induced apoptosis. We found that the induced apoptosis was accompanied by a series of biochemical events, including intracellular ceramide generation, PP2A activation, Akt dephosphorylation, Mcl-1 and FLICE inhibiting protein (FLIP) transcriptional downregulation, Bax mitochondrial distribution, and caspase 3 activation...
April 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29464081/dapk-and-cip2a-are-involved-in-gas6-axl-mediated-schwann-cell-proliferation-in-a-rat-model-of-bilateral-cavernous-nerve-injury
#15
Yen-Lin Chen, Yi-Ting Tsai, Ting-Ting Chao, Yi-No Wu, Meng-Chuan Chen, Ying-Hung Lin, Chun-Hou Liao, Shang-Shing P Chou, Han-Sun Chiang
Purpose: Impotence is one of the major complications occurring in prostate cancer patients after radical prostectomy (RP). Self-repair of the injured nerve has been observed in animal models and in patients after RP. However, the downstream signalling is not well documented. Here, we found that the DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. Materials and Methods: The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury (BCNI) group and a 28-day post-BCNI group...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29462574/adiponectin-receptor-agonist-adiporon-decreased-ceramide-and-lipotoxicity-and-ameliorated-diabetic-nephropathy
#16
Sun Ryoung Choi, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Beom Soon Choi, Yong-Soo Kim, Hye Won Kim, Kyung-Min Lim, Min Jeong Kim, Cheol Whee Park
BACKGROUND: Adiponectin is known to take part in the regulation of energy metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications. Among the lipid metabolites, the ceramide subspecies of sphingolipids have been linked to features of lipotoxicity, including inflammation, cell death, and insulin resistance. We investigated the role of AdipoRon in the prevention and development of type 2 diabetic nephropathy...
February 17, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29455644/mir-19b-enhances-proliferation-and-apoptosis-resistance-via-the-egfr-signaling-pathway-by-targeting-pp2a-and-bim-in-non-small-cell-lung-cancer
#17
Ulrich Baumgartner, Fabienne Berger, Ali Hashemi Gheinani, Sabrina Sofia Burgener, Katia Monastyrskaya, Erik Vassella
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29398519/compound-c-enhances-tau-phosphorylation-at-serine-396-via-pi3k-activation-in-an-ampk-and-rapamycin-independent-way-in-differentiated-sh-sy5y-cells
#18
Shohreh Majd, Simon Koblar, John Power
Aggregation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFT) is a main hallmark for Alzheimer's disease (AD). Activation of cellular metabolic axis, made of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) have been implicated in generating tau pathology of AD. Thus, blocking either of these two proteins or both, are suggested as the future therapeutic approaches for AD. How and to what level these approaches could be applied, however are not entirely clear...
March 23, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29393542/cucurbitacin-b-induces-inhibitory-effects-via-cip2a-pp2a-akt-pathway-in-glioblastoma-multiforme
#19
Shanshan Qin, Jing Li, Yuan Si, Zhongwei He, Te Zhang, Dawei Wang, Xuewen Liu, Yang Guo, Liang Zhang, Shan Li, Qiang Li, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple types of tumors and promotes the proliferation and transformation of cancer cells. However, whether CIP2A can be a new drug target for human glioblastoma multiforme (GBM) is largely unclear. In the present study, we demonstrated that the overexpression of CIP2A promotes invasive behavior in GBM, and a natural compound, cucurbitacin B (CuB), shows an anti-proliferative and anti-invasion effect in GBM cell lines...
June 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29385539/foxg1-overexpression-in-neocortical-pyramids-stimulates-dendrite-elongation-via-hes1-and-pcreb1-upregulation
#20
Simone Chiola, Mihn Duc Do, Lucy Centrone, Antonello Mallamaci
The architecture of neocortical projection neurons is subject of a complex gene control. Here we demonstrated that Foxg1, a transcription factor gene which patterns the early rostral brain and sets the pace of telencephalic neuronogenesis, specifically stimulates dendrite elongation. This phenomenon occurs in vivo like in vitro, and it is detectable even upon moderate changes of Foxg1 expression levels. We found that Foxg1 acts by stimulating Hes1, which in turn upregulates pCreb1, a well-known pro-dendritogenic effector, and downregulates Syt and Ndr1, namely two established antagonizers of dendrite elongation...
January 28, 2018: Cerebral Cortex
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