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https://www.readbyqxmd.com/read/28410423/daf-18-pten-signals-through-aak-1-ampk-to-inhibit-mpk-1-mapk-in-feedback-control-of-germline-stem-cell-proliferation
#1
Patrick Narbonne, Paul S Maddox, Jean-Claude Labbé
Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS) and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C...
April 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28409350/primary-cilia-in-cystic-kidney-disease
#2
Prachee Avasthi, Robin L Maser, Pamela V Tran
Primary cilia are small, antenna-like structures that detect mechanical and chemical cues and transduce extracellular signals. While mammalian primary cilia were first reported in the late 1800s, scientific interest in these sensory organelles has burgeoned since the beginning of the twenty-first century with recognition that primary cilia are essential to human health. Among the most common clinical manifestations of ciliary dysfunction are renal cysts. The molecular mechanisms underlying renal cystogenesis are complex, involving multiple aberrant cellular processes and signaling pathways, while initiating molecular events remain undefined...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28397012/live-kinase-b1-maintains-cd34-cd38-aml-cell-proliferation-and-self-renewal
#3
Huihan Wang, Xiaobin Wang, Na Xin, Lin Qi, Aijun Liao, Wei Yang, Zhuogang Liu, Chenghai Zhao
Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34(+)CD38(-) fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34(+)CD38(-) AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34(+)CD38(-) AML cells, induced CD34(+)CD38(-) AML cells into G2/M phase, and enhanced the sensitivity of CD34(+)CD38(-) AML cells to chemotherapy...
April 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28391433/a-peutz-jeghers-syndrome-family-associated-with-sinonasal-adenocarcinoma-28-years-follow-up-report
#4
Jy-Ming Chiang, Tse-Ching Chen
Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in both of the gastrointestinal tract and mucosal pigmentation. It could increase in risk of intestinal and extra-intestinal neoplasms. We here described three cases of sinonasal polyposis in a PJS family and two developed sinonasal type adenocarcinoma. Genetic study revealed a germline STK11/LKB1 mutation on codon 179 (c.C536G, p.P179R) of exon 4. LOH analysis of the LKB1 locus confirms this to be a deleterious mutation...
April 8, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28391030/metformin-triggers-autophagy-to-attenuate-drug-induced-apoptosis-in-nsclc-cells-with-minor-effects-on-tumors-of-diabetic-patients
#5
Zhiguang Xiao, Silvia Gaertner, Alicia Morresi-Hauf, Rebecca Genzel, Thomas Duell, Axel Ullrich, Pjotr G Knyazev
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background...
April 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28387316/lkb1-inactivation-drives-lung-cancer-lineage-switching-governed-by-polycomb-repressive-complex-2
#6
Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-de-Alba, Margherita Paschini, Grit S Herter-Sprie, Gang Lu, Xin Zhang, Bryan P Marsh, Stephanie J Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M Sholl, Anil K Rustgi, David J Kwiatkowski, J Alan Diehl, Adam J Bass, Norman E Sharpless, Glenn Dranoff, Peter S Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F Kim, Kwok-Kin Wong
Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28386315/protective-benefits-of-amp-activated-protein-kinase-in-hepatic-ischemia-reperfusion-injury
#7
REVIEW
Min Zhang, Dan Yang, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Li Zhang
Hepatic ischemia-reperfusion injury (HIRI) is a major cause of hepatic failure and death after liver trauma, haemorrhagic shock, resection surgery and liver transplantation. AMP-activated protein kinase (AMPK) is an energy sensitive kinase that plays crucial roles in the regulation of metabolic homeostasis. In HIRI, ischemia induces the decline of ATP and the increased ratio of AMP/ATP, which promotes the phosphorylation and activation of AMPK. Three AMPK kinases, liver kinase B1 (LKB1), Ca(2+)/calmodulin-depedent protein kinase kinase β (CaMKKβ) and TGF-β-activated kinase-1 (TAK1), are main upstream kinases for the phosphorylation of AMPK...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28382150/mir-93-promotes-tumorigenesis-and-metastasis-of-non-small-cell-lung-cancer-cells-by-activating-the-pi3k-akt-pathway-via-inhibition-of-lkb1-pten-cdkn1a
#8
Chunmei Li, Jianxin Lyu, Qing H Meng
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of clinical lung cancer cases. MicroRNA-93 (miR-93) is an oncomiR in many types of human cancer, exerting pivotal effects in the development and progression of malignancies, including NSCLC. However, the mechanism underlying miR-93 involvement in NSCLC is unknown. Our purpose was to reveal and explain this mechanism, with the goal of contributing to the development of new diagnostic biomarkers and individualized therapeutic tools...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28376202/role-of-cps1-in-cell-growth-metabolism-and-prognosis-in-lkb1-inactivated-lung-adenocarcinoma
#9
Müge Çeliktas, Ichidai Tanaka, Satyendra Chandra Tripathi, Johannes F Fahrmann, Clemente Aguilar-Bonavides, Pamela Villalobos, Oliver Delgado, Dilsher Dhillon, Jennifer B Dennison, Edwin J Ostrin, Hong Wang, Carmen Behrens, Kim-Anh Do, Adi F Gazdar, Samir M Hanash, Ayumu Taguchi
Background: Liver kinase B1 ( LKB1 ) is a tumor suppressor in lung adenocarcinoma (LADC). We investigated the proteomic profiles of 45 LADC cell lines with and without LKB1 inactivation. Carbamoyl phosphate synthetase 1 (CPS1), the first rate-limiting mitochondrial enzyme in the urea cycle, was distinctively overexpressed in LKB1-inactivated LADC cell lines. We therefore assessed the role of CPS1 and its clinical relevance in LKB1-inactivated LADC. Methods: Mass spectrometric profiling of proteome and metabolome and function of CPS1 were analyzed in LADC cell lines...
March 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28368277/structure-of-the-complex-of-phosphorylated-liver-kinase-b1-and-14-3-3%C3%AE
#10
Yongjian Lu, Sheng Ding, Ruiqing Zhou, Jianyong Wu
The serine/threonine protein kinase liver kinase B1 (LKB1) is a tumour suppressor and plays important roles in development and metabolism. It phosphorylates AMPK and AMPK-related kinases to regulate multiple physiological processes. Mutations in LKB1 often occur in multiple cancers. LKB1 can be suppressed by 14-3-3 proteins in a phosphorylation-dependent manner. Previously, the structure of a 14-3-3ζ-LKB1 fusion protein has been reported, revealing a phosphorylation-independent binding mode of LKB1 to 14-3-3 proteins...
April 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28360860/acanthoic-acid-can-partially-prevent-alcohol-exposure-induced-liver-lipid-deposition-and-inflammation
#11
You-Li Yao, Xin Han, Zhi-Man Li, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu
Aims: The present study aims to detect the effect of acanthoic acid (AA) on alcohol exposure-induced liver lipid deposition and inflammation, and to explore the mechanisms. Methods: C57BL/6 mice were pretreated with single dose of AA (20 and 40 mg/kg) by oral gavage or equal volume of saline, and then exposed to three doses of ethanol (5 g/kg body weight, 25%, w/v) by gavage within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing. Serum and hepatic indexes were detected by western blot, RT-PCR, and histopathological assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28351375/erratum-to-honokiol-activates-amp-activated-protein-kinase-in-breast-cancer-cells-via-lkb1-dependent-pathway-and-inhibits-breast-carcinogenesis
#12
Arumugam Nagalingam, Jack L Arbiser, Michael Y Bonner, Neeraj K Saxena, Dipali Sharma
No abstract text is available yet for this article.
March 28, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28349253/mangiferin-suppresses-endoplasmic-reticulum-stress-in-perivascular-adipose-tissue-and-prevents-insulin-resistance-in-the-endothelium
#13
Xiaoshan Xu, Yupeng Chen, Junna Song, Fangjie Hou, Xuelian Ma, Baolin Liu, Fang Huang
PURPOSE: Mangiferin is a naturally occurring glucosylxanthone with beneficial effects on glucose and lipid homeostasis. This study investigates the potential therapeutic effect of Mangiferin in perivascular adipose tissue (PVAT) and whether it contributes to regulating insulin action in the endothelium. METHODS: Palmitate challenge evoked ROS-associated endoplasmic reticulum stress (ER stress) and NLRP3 inflammasome activation in PVAT. The conditioned medium from PA-stimulated PVAT was prepared to induce endothelial insulin resistance, and improved endothelium-dependent vasodilation in response to insulin was detected in vitro and in vivo...
March 27, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28346429/deletion-of-endothelial-cell-specific-liver-kinase-b1-increases-angiogenesis-and-tumor-growth-via-vascular-endothelial-growth-factor
#14
W Zhang, Y Ding, C Zhang, Q Lu, Z Liu, K Coughlan, I Okon, M-H Zou
Liver kinase B1 (LKB1) is a serine/threonine protein kinase ubiquitously expressed in mammalian cells. It was first identified in Peutz-Jeghers syndrome as a tumor suppressor gene. Whether endothelial LKB1 regulates angiogenesis and tumor growth is unknown. In this study, we generated endothelial cell-specific LKB1-knockout (LKB1(endo-/-)) mice by crossbreeding vascular endothelial-cadherin-Cre mice with LKB1(flox/flox) mice. Vascular endothelial growth factor (VEGF) level was highly co-stained in endothelial cells but not in macrophages in LKB1(endo-/-) mice...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28343145/effects-of-tiletamine-on-the-adenosine-monophosphate-activated-protein-kinase-signaling-pathway-in-the-rat-central-nervous-system
#15
Li-Xue Su, Xing-Xing Shi, Peng Yang, Hao Chen, Xin Li, Hong-Gang Fan, Hong-Bin Wang
OBJECTIVE: The dissociative anesthetic tiletamine, which acts on the central nervous system (CNS), is widely used in veterinary medicine and animal experiments. Recent studies indicate that adenosine 5'-monophosphate activated protein kinase (AMPK) plays a key role in the analgesic action of tiletamine. In the present study, the effects of tiletamine on the AMPK signaling pathway in rats were investigated. METHODS: Sprague-Dawley rats were injected intraperitoneally with tiletamine and executed at 10, 20, 40 and 60min post injection...
March 21, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28299850/ethanol-extract-of-pinus-koraiensis-leaf-ameliorates-alcoholic-fatty-liver-via-the-activation-of-lkb1-ampk-signaling-in-vitro-and-in-vivo
#16
Sang-Hyuk Hong, Hyemin Lee, Hyo-Jung Lee, Bonglee Kim, Min-Ho Nam, Bum-Sang Shim, Sung-Hoon Kim
Although Pinus koraiensis leaf (PKL) was reported for its anti-diabetes, anti-obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP-activated protein kinase signaling, low-density lipoprotein receptor and decreased fatty acid biosynthesis-related proteins such as sterol regulatory element-binding protein 1c, fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells...
March 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28289710/targeting-adhesion-signaling-in-kras-lkb1-mutant-lung-adenocarcinoma
#17
Melissa Gilbert-Ross, Jessica Konen, Junghui Koo, John Shupe, Brian S Robinson, Walter Guy Wiles, Chunzi Huang, W David Martin, Madhusmita Behera, Geoffrey H Smith, Charles E Hill, Michael R Rossi, Gabriel L Sica, Manali Rupji, Zhengjia Chen, Jeanne Kowalski, Andrea L Kasinski, Suresh S Ramalingam, Haian Fu, Fadlo R Khuri, Wei Zhou, Adam I Marcus
Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289208/specific-deletion-of-lkb1-stk11-in-the-m%C3%A3-llerian-duct-mesenchyme-drives-hyperplasia-of-the-periurethral-stroma-and-tumorigenesis-in-male-mice
#18
Jitu W George, Amanda L Patterson, Pradeep S Tanwar, André Kajdacsy-Balla, Gail S Prins, Jose M Teixeira
Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11(CKO) mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28253973/methods-to-study-lysosomal-ampk-activation
#19
C-S Zhang, M Li, S-C Lin
The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis. It is activated by the upstream kinase LKB1 (liver kinase B1) when the AMP/ATP ratio is increased during starvation or heightened exercises. Based on reconstitution experiments using purified individual proteins, AMPK was demonstrated to be directly phosphorylated on its conserved residue Thr172 by LKB1, which was promoted by increased levels of AMP. However, recent studies have engendered a paradigm shift for how AMPK is activated inside the cell or animal tissues, unraveling that AXIN binds to LKB1 and tethers it to AMPK located on the surface of late endosome and lysosome (hereafter, only lysosome is discussed) in response to glucose starvation...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28230853/mesenchymal-stromal-cells-inhibit-cd25-expression-via-the-mtor-pathway-to-potentiate-t-cell-suppression
#20
Hyun Seung Yoo, Kyuheon Lee, Kwangmin Na, Yong Xu Zhang, Hyun-Ja Lim, TacGhee Yi, Sun U Song, Myung-Shin Jeon
Mesenchymal stromal cells (MSCs) are known to suppress T-cell activation and proliferation. Several studies have reported that MSCs suppress CD25 expression in T cells. However, the molecular mechanism underlying MSC-mediated suppression of CD25 expression has not been fully examined. Here, we investigated the mTOR pathway, which is involved in CD25 expression in T cells. We showed that MSCs inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase (iNOS) inhibitor...
February 23, 2017: Cell Death & Disease
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