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https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#1
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28504720/a-clinical-drug-library-screen-identifies-clobetasol-propionate-as-an-nrf2-inhibitor-with-potential-therapeutic-efficacy-in-keap1-mutant-lung-cancer
#2
E-J Choi, B-J Jung, S-H Lee, H-S Yoo, E-A Shin, H-J Ko, S Chang, S-Y Kim, S-M Jeon
The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28499784/gsk-3-as-a-novel-prognostic-indicator-in-leukemia
#3
REVIEW
Peter P Ruvolo
While leukemias represent a diverse set of diseases with malignant cells derived from myeloid or lymphoid origin, a common feature is the dysregulation of signal transduction pathways that influence leukemogeneisis, promote drug resistance, and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream regulators can activate the AKT kinase which has central roles in supporting cell proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3 (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of metabolism but emerged as central players in cancer in the early 1990s...
May 8, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28486050/the-cdk4-6-inhibitor-palbociclib-synergizes-with-irinotecan-to-promote-colorectal-cancer-cell-death-under-hypoxia
#4
Jun Zhang, Lanlan Zhou, Shuai Zhao, David T Dicker, Wafik S El-Deiry
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK3-β. In order to translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia...
May 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28483921/lack-of-liver-glycogen-causes-hepatic-insulin-resistance-and-steatosis-in-mice
#5
Jose M Irimia, Catalina M Meyer, Dyann M Segvich, Sneha Surendran, Anna A DePaoli-Roach, Nuria Morral, Peter J Roach
Disruption of the Gys2 gene that encodes the liver isoform of glycogen synthase generates a mouse (LGSKO mouse) with an almost complete lack of hepatic glycogen, impaired glucose disposal and a pre-disposition to enter the fasted state. This study explores how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice is reduced in liver, but not in muscle, suggesting an organ specific defect. Phosphorylation of several components of the hepatic insulin signaling pathway, IRS1, Akt, and GSK3, were decreased in LGSKO mice and, after insulin stimulation, their responses were significantly suppressed, both temporally and in an insulin dose response...
May 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28471233/effect-of-sodium-aescinate-treatment-on-pcos-rat-model-with-insulin-resistance
#6
L Chen, L M Hu, Y F Wang, H Y Yang, X Y Huang, W Zhou, H X Sun
BACKGROUND: Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. OBJECTIVE: To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. METHODS: Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12)...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28468511/vitex-rotundifolia-fruit-extract-induces-apoptosis-through-the-downregulation-of-atf3-mediated-bcl-2-expression-in-human-colorectal-cancer-cells
#7
Hun Min Song, Gwang Hun Park, Jin Suk Koo, Hyung Jin Jeong, Jin Boo Jeong
Fruit from Vitex rotundifolia L. (VF) has been reported to initiate apoptosis in human colorectal cancer cells through the accumulation of reactive oxygen species. Since various regulatory factors are involved in the apoptotic pathway, further study of the potential mechanisms of VF associated with the induction of apoptosis may be important despite the fact that the molecular target of VF for apoptosis has already been elucidated. In this study, we showed a new potential mechanism for the relationship between VF-mediated ATF3 expression and apoptosis to better understand the apoptotic mechanism of VF in human colorectal cancer cells...
May 3, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28461660/derivation-of-mouse-embryonic-stem-es-cell-lines-using-small-molecule-inhibitors-of-erk-and-gsk3-signaling-2i
#8
Jennifer Nichols, Kenneth Jones
The efficiency of embryonic stem (ES) cell derivation is very high if embryos are incubated, from the eight-cell stage, in the presence of the two inhibitors of signaling via the Erk and Gsk3 pathways (PD0325901 and CHIR99021, respectively, known as "2i"). The success rate may vary, depending on the quality of the embryos and the speed with which they are processed, but it is not unusual to obtain ES cell lines from all embryos allocated to the study, even from the least permissive strains. Furthermore, ES cells can be efficiently obtained from any complex genetic mouse model or for in vitro analysis and additional genetic manipulation in any background of choice...
May 1, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28457889/2i-maintains-a-naive-ground-state-in-escs-through-two-distinct-epigenetic-mechanisms
#9
Ye-Ji Sim, Min-Seong Kim, Abeer Nayfeh, Ye-Jin Yun, Su-Jin Kim, Kyung-Tae Park, Chang-Hoon Kim, Kye-Seong Kim
Mouse embryonic stem cells (ESCs) are maintained in serum with leukemia inhibitory factor (LIF) to maintain self-renewal and pluripotency. Recently, a 2i culture method was reported using a combination of MEK inhibition (MEKi) and GSK3 inhibition (GSK3i) with LIF to maintain ESCs in a naive ground state. How 2i maintains a ground state of ESCs remains elusive. Here we show that MEKi and GSK3i maintain the ESC ground state by downregulating global DNA methylation through two distinct mechanisms. MEK1 phosphorylates JMJD2C for ubiquitin-mediated protein degradation...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28456524/protein-kinases-in-pluripotency-beyond-the-usual-suspects
#10
REVIEW
Rosalia Fernandez-Alonso, Francisco Bustos, Charles A C Williams, Greg M Findlay
Post-translational modification of proteins by phosphorylation plays a key role in regulating all aspects of eukaryotic biology. Embryonic Stem Cell (ESC) pluripotency, defined as the ability to differentiate into all cell types in the adult body, is no exception. Maintenance and dissolution of pluripotency is tightly controlled by phosphorylation. As a result, key signalling pathways that regulate pluripotency have been identified and their functions well characterised. Amongst the best studied are the FGF-ERK1/2 pathway, PI3K-AKT, the LIF-JAK-STAT3 axis, WNT-GSK3 signalling and the TGFβ/BMP family...
April 26, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28449557/wnt-and-gsk3-signaling-pathways-in-bipolar-disorder-clinical-and-therapeutic-implications
#11
REVIEW
Ather Muneer
The neurobiology of bipolar disorder, a chronic and systemic ailment is not completely understood. The bipolar phenotype manifests in myriad ways, and psychopharmacological agents like lithium have long term beneficial effects. The enzyme glycogen synthase kinase 3 (GSK3) has come into focus, as lithium and several other mood stabilizing medications inhibit its activity. This kinase and its key upstream modulator, Wnt are dysregulated in mood disorders and there is a growing impetus to delineate the chief substrates involved in the development of these illnesses...
May 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28440874/role-of-glycogen-synthase-kinase-3-in-ischemia-induced-blood-brain-barrier-disruption-in-aged-female-rats
#12
Han Xiao, Mingyang Deng, Binbin Yang, Jianguang Tang, Zhiping Hu
Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO)...
April 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#13
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28428626/c1qbp-suppresses-cell-adhesion-and-metastasis-of-renal-carcinoma-cells
#14
Yong Wang, Donghe Fu, Jing Su, Yajing Chen, Can Qi, Yin Sun, Yuanjie Niu, Ning Zhang, Dan Yue
Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424497/the-glycogen-synthase-kinase-mogsk1-regulated-by-mps1-map-kinase-is-required-for-fungal-development-and-pathogenicity-in-magnaporthe-oryzae
#15
Tengsheng Zhou, Yasin F Dagdas, Xiaohan Zhu, Shiqin Zheng, Liqiong Chen, Zachary Cartwright, Nicholas J Talbot, Zonghua Wang
Magnaporthe oryzae, the causal agent of blast disease, is one of the most destructive plant pathogens, causing significant yield losses on staple crops such as rice and wheat. The fungus infects plants with a specialized cell called an appressorium, whose development is tightly regulated by MAPK signaling pathways following the activation of upstream sensors in response to environmental stimuli. Here, we show the expression of the Glycogen synthase kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly under the stressed conditions...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423622/hnrnpk-mir-223-fbxw7-feedback-cascade-promotes-pancreatic-cancer-cell-growth-and-invasion
#16
D He, Cheng Huang, Qingxin Zhou, Dawei Liu, Longhui Xiong, Hongxia Xiang, Guangnian Ma, Zhiyong Zhang
Several studies have identified miR-223 critically involved in various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action and regulatory mechanisms in PDAC remains largely unclear. In this study, we found that the expression levels of miR-223 were increased in clinical samples with PDAC (81.6%). The upregulation of miR-223 increases the proliferation, migration, and invasive abilities of PDAC cells in vitro and in vivo. Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7 reverted miR-223- induced drastic proliferation in PDAC cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423582/parthenolide-suppresses-non-small-cell-lung-cancer-glc-82-cells-growth-via-b-raf-mapk-erk-pathway
#17
Minting Lin, Hong Bi, Yanyan Yan, Wenjing Huang, Guiping Zhang, Genshui Zhang, Sili Tang, Yun Liu, Lingling Zhang, Jinxiang Ma, Jianye Zhang
Non-small cell lung cancer (NSCLC), one type of lung cancer, owns high rates of morbidity and mortality. B-Raf is one of the promising oncogenic drivers of NSCLC. Parthenolide, a natural product, is mainly extracted from the herbal plant Tanacetum parthenium. The effect of parthenolide on NSCLC cells and its potential as B-Raf inhibitor were studied in this study. It's shown that parthenolide exhibited the strong cytotoxicity against NSCLC cells with IC50 ranging from 6.07 ± 0.45 to 15.38 ± 1.13 μM. Parthenolide was also able to induce apoptosis, suppress proliferation and invasion in NSCLC cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421542/neural-stem-cell-transplantation-promotes-functional-recovery-from-traumatic-brain-injury-via-brain-derived-neurotrophic-factor-mediated-neuroplasticity
#18
Liu-Lin Xiong, Yue Hu, Piao Zhang, Zhuo Zhang, Li-Hong Li, Guo-Dong Gao, Xin-Fu Zhou, Ting-Hua Wang
Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10(5)/μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28418862/niclosamide-is-a-potential-therapeutic-for-familial-adenomatosis-polyposis-by-disrupting-axin-gsk3-interaction
#19
Sung Yong Ahn, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Ji Hye Yang, So Young Cha, Eunae Sandra Cho, Yoonmi Lee, Jeong Seok Cha, Hyun Soo Cho, Yoon Jeon, Young-Su Yuk, Suebean Cho, Kyoung Tai No, Hyun Sil Kim, Ho Lee, Jiwon Choi, Jong In Yook
The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414160/paraquat-induces-extrinsic-pathway-of-apoptosis-in-a549-cells-by-induction-of-dr5-and-repression-of-anti-apoptotic-proteins-ddx3-and-gsk3-expression
#20
Sasiphen Hathaichoti, Daranee Visitnonthachai, Pronrumpa Ngamsiri, Apichaya Niyomchan, Oyu Tsogtbayar, Churaibhon Wisessaowapak, Piyajit Watcharasit, Jutamaad Satayavivad
Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity partly through induction of apoptosis. Here we demonstrated that PQ caused apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating caspase-8 activation and truncated Bid, the two key mediators of extrinsic apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor-5) and caspase-8 interaction, indicating formation of DISC (death-inducing signaling complex). These results indicate that PQ induces apoptosis through extrinsic pathway in A549 cells...
April 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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