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https://www.readbyqxmd.com/read/29352002/intestinal-epithelial-cell-derived-lkb1-suppresses-colitogenic-microbiota
#1
Xia'nan Liu, Jinfeng Lu, Zhenshan Liu, Junjie Zhao, Hongxiang Sun, Ningbo Wu, Hongzhi Liu, Weiwei Liu, Zhuqin Hu, Guangxun Meng, Lei Shen, Aaron W Miller, Bing Su, Xiaoxia Li, Zizhen Kang
Dysregulation of the immune barrier function of the intestinal epithelium can often result in dysbiosis. In this study we report a novel role of intestinal epithelial cell (IEC) -derived liver kinase B1 (LKB1) in suppressing colitogenic microbiota. IEC-specific deletion of LKB1 (LKB1ΔIEC) resulted in an increased susceptibility to dextran sodium sulfate (DSS)-induced colitis and a definitive shift in the composition of the microbial population in the mouse intestine. Importantly, transfer of the microbiota from LKB1ΔIEC mice was sufficient to confer increased susceptibility to DSS-induced colitis in wild-type recipient mice...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343420/ampk-re-activation-suppresses-hepatic-steatosis-but-its-downregulation-does-not-promote-fatty-liver-development
#2
Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, Marc Foretz
Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism...
January 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29338075/lkb1-ampk-mediated-regulation-by-gentiopicroside-ameliorates-p2x7r-dependent-alcoholic-hepatosteatosis
#3
Xia Li, Yu Zhang, Quan Jin, Kai-Li Xia, Min Jiang, Ben-Wen Cui, Yan-Ling Wu, Shun-Zong Song, Li-Hua Lian, Ji-Xing Nan
BACKGROUND AND PURPOSE: Regulating P2x7R-NLRP3 inflammasome activation might be a potential therapeutic strategy to treat alcoholic hepatosteatosis. We investigated whether this process would be modulated by gentiopicroside (GPS), which is the main active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were established by intragastrically administrated ethanol or using chronic plus binge ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice...
January 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#4
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
January 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29305497/glutaminolysis-drives-lung-cancer-metastasis-via-the-plag1-gdh1-axis
#5
(no author information available yet)
PLAG1-mediated GDH1 upregulation promotes LKB1-deficient lung cancer anoikis resistance.
January 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29304329/glutamate-dehydrogenase-to-the-rescue
#6
Jonathan L Coloff
Tumor cell metabolism can be altered to support specific pathological functions or to adapt to environmental stresses. In this issue of Molecular Cell, Jin et al. (2018) identify induction of glutamate dehydrogenase as a critical metabolic adaptation in matrix-detached cancer cells that is required for metastasis of LKB1-deficient lung tumors.
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29302794/evaluation-of-the-neuroprotective-effect-of-sirt3-in-experimental-stroke
#7
Rajkumar Verma, Rodney M Ritzel, Joshua Crapser, Brett D Friedler, Louise D McCullough
Sirtuins (Sirt) are a family of NAD+ dependent histone deacetylase (HDAC) proteins implicated in aging, cell cycle regulation, and metabolism. These proteins are involved in the epigenetic modification of neuromodulatory proteins after strokevia acetylation/deacetylation. The specific role of Sirt3, a mitochondrial sirtuin, in post-stroke injury has been relatively unexplored. Using male Sirt3 knockout (KO) mice and wild-type littermates (WT), we show that Sirt3 KO mice show significant neuroprotection at 3 days after ischemia/reperfusion (I/R) or stroke injury...
January 4, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#8
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29289437/ampk-and-friends-central-regulators-of-%C3%AE-cell-biology
#9
REVIEW
Jillian L Rourke, Queenie Hu, Robert A Screaton
If left unchecked, prediabetic hyperglycemia can progress to diabetes and often life-threatening attendant secondary complications. Central to the process of glucose homeostasis are pancreatic β cells, which sense elevations in plasma glucose and additional dietary components and respond by releasing the appropriate quantity of insulin, ensuring the arrest of hepatic glucose output and glucose uptake in peripheral tissues. Given that β cell failure is associated with the transition from prediabetes to diabetes, improved β cell function ('compensation') has a central role in preventing type 2 diabetes mellitus (T2DM)...
December 27, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29249655/the-plag1-gdh1-axis-promotes-anoikis-resistance-and-tumor-metastasis-through-camkk2-ampk-signaling-in-lkb1-deficient-lung-cancer
#10
Lingtao Jin, Jaemoo Chun, Chaoyun Pan, Avi Kumar, Guojing Zhang, Youna Ha, Dan Li, Gina N Alesi, Yibin Kang, Lu Zhou, Wen-Mei Yu, Kelly R Magliocca, Fadlo R Khuri, Cheng-Kui Qu, Christian Metallo, Taofeek K Owonikoko, Sumin Kang
Loss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance...
December 12, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29228674/the-regulatory-role-of-aberrant-phosphatase-and-tensin-homologue-and-liver-kinase-b1-on-akt-mtor-c-myc-axis-in-pancreatic-neuroendocrine-tumors
#11
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
Pancreatic neuroendocrine tumor (pNET) is an uncommon type of pancreatic neoplasm. Low Phosphatase and Tensin Homologue (PTEN) expression and activation of the mechanistic target of rapamycin (mTOR) pathway have been noted in pNETs, and the former is associated with poor survival in pNET patients. Based on the results of the RADIANT-3 study, everolimus, an oral mTOR inhibitor, has been approved to treat advanced pNETs. However, the exact regulatory mechanism for the mTOR pathway in pNETs remains largely unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223537/rankl-signaling-sustains-primary-tumor-growth-in-genetically-engineered-mouse-models-of-lung-adenocarcinoma
#12
Julien Faget, Caroline Contat, Nadine Zangger, Solange Peters, Etienne Meylan
HYPOTHESIS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. METHODS: RANK and RANKL expression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography...
December 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29208669/vimentin-is-required-for-lung-adenocarcinoma-metastasis-via-heterotypic-tumor-cell-cancer-associated-fibroblast-interactions-during-collective-invasion
#13
Alessandra M Richardson, Lauren Havel, Allyson E Koyen, Jessica M Konen, John A Shupe, W G Wiles, W David Martin, Hans Grossniklaus, Gabriel L Sica, Melissa Gilbert-Ross, Adam Marcus
PURPOSE: Vimentin is an epithelial to mesenchymal transition (EMT) biomarker and intermediate filament protein that functions during cell migration to maintain structure and motility. Despite the abundance of clinical data linking vimentin to poor patient outcome, it is unclear if vimentin is required for metastasis or is a correlative biomarker. We developed a novel genetically engineered mouse model (GEMM) to probe vimentin in lung adenocarcinoma metastasis. EXPERIMENTAL DESIGN: We used the LSL-Kras G12D/Lkb1 fl/fl/Vim-/-model (KLV-/-), which incorporates a whole-body knockout of vimentin and is derived from the Cre-dependent LSL-Kras G12D/Lkb1 fl/fl model (KLV+/+)...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29202476/stromal-lkb1-deficiency-leads-to-gastrointestinal-tumorigenesis-involving-the-il-11-jak-stat3-pathway
#14
Saara Ollila, Eva Domènech-Moreno, Kaisa Laajanen, Iris Pl Wong, Sushil Tripathi, Nalle Pentinmikko, Yajing Gao, Yan Yan, Elina H Niemelä, Timothy C Wang, Benoit Viollet, Gustavo Leone, Pekka Katajisto, Kari Vaahtomeri, Tomi P Mäkelä
Germline mutations in the gene encoding tumor suppressor kinase LKB1 lead to gastrointestinal tumorigenesis in Peutz-Jeghers syndrome (PJS) patients and mouse models; however, the cell types and signaling pathways underlying tumor formation are unknown. Here, we demonstrated that mesenchymal progenitor- or stromal fibroblast-specific deletion of Lkb1 results in fully penetrant polyposis in mice. Lineage tracing and immunohistochemical analyses revealed clonal expansion of Lkb1-deficient myofibroblast-like cell foci in the tumor stroma...
December 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29191602/lkb1-stk11-mutations-in-non-small-cell-lung-cancer-patients-descriptive-analysis-and-prognostic-value
#15
Francesco Facchinetti, Maria Virginia Bluthgen, Gabrielle Tergemina-Clain, Laura Faivre, Jean-Pierre Pignon, David Planchard, Jordi Remon, Jean-Charles Soria, Ludovic Lacroix, Benjamin Besse
BACKGROUND: LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet. MATERIALS AND METHODS: This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29186696/a-highly-sensitive-fret-biosensor-for-ampk-exhibits-heterogeneous-ampk-responses-among-cells-and-organs
#16
Yumi Konagaya, Kenta Terai, Yusuke Hirao, Kanako Takakura, Masamichi Imajo, Yuji Kamioka, Norio Sasaoka, Akira Kakizuka, Kenta Sumiyama, Tomoichiro Asano, Michiyuki Matsuda
AMP-activated protein kinase (AMPK), a master regulator of cellular metabolism, is a potential target for type 2 diabetes. Although extensive in vitro studies have revealed the complex regulation of AMPK, much remains unknown about the regulation in vivo. We therefore developed transgenic mice expressing a highly sensitive fluorescence resonance energy transfer (FRET)-based biosensor for AMPK, called AMPKAR-EV. AMPKAR-EV allowed us to readily examine the role of LKB1, a canonical stimulator of AMPK, in drug-induced activation and inactivation of AMPK in vitro...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29175669/euterpe-oleracea-mart-a%C3%A3-a%C3%A3-seed-extract-associated-with-exercise-training-reduces-hepatic-steatosis-in-type-2-diabetic-male-rats
#17
Graziele Freitas de Bem, Cristiane Aguiar da Costa, Viviane da Silva Cristino Cordeiro, Izabelle Barcellos Santos, Lenize Costa Reis Marins de Carvalho, Ricardo de Andrade Soares, Jéssica Honorato Ribeiro, Marcelo Augusto Vieira de Souza, Pergentino José da Cunha Sousa, Dayane Teixeira Ognibene, Angela Castro Resende, Roberto Soares de Moura
Type 2 diabetes mellitus contributes to an increased risk of metabolic and morphological changes in key organs, such as the liver. We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on hepatic steatosis induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks, followed by a single low dose of STZ (35 mg/kg i.p.). Control and diabetic groups were subdivided into four groups that were fed with standard chow diet for 4 weeks...
October 13, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29171745/retracted-resveratrol-inhibits-oesophageal-adenocarcinoma-cell-proliferation-via-amp-activated-protein-kinase-signaling
#18
(no author information available yet)
Retraction: Retracted:Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via AMP-activated protein kinase signaling Asian Pacific Journal of Cancer Prevention (APJCP) has retracted the article titled “Resveratrol Inhibits Oesophageal Adenocarcinoma Cell Proliferation via AMP-activated Protein Kinase Signaling”(1) for reason of having duplicated contents brought to the attention of APJCP’s editorial office by the following email content: “Dear Editors of Gastroenterology and Hepatology, Acta Pharmacologica Sinica, Asian Pac J Cancer Prev, Clinical and Experimental Hypertension, I write to you from the editorial office of PLOS ONE to inform you of concerns related to duplicated content in articles published by your journals...
November 24, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29169176/ablation-of-atg4b-suppressed-autophagy-and-activated-ampk-for-cell-cycle-arrest-in-cancer-cells
#19
Pei-Feng Liu, Chien-Jen Hsu, Wei-Lun Tsai, Jin-Shiung Cheng, Jih-Jung Chen, I-Fei Huang, Ho-Hsing Tseng, Hsueh-Wei Chang, Chih-Wen Shu
BACKGROUND/AIMS: ATG4B is a cysteine protease required for autophagy, which is a cellular catabolic pathway involved in energy balance. ATG4B expression is elevated during tumor growth in certain types of cancer, suggesting that ATG4B is an attractive target for cancer therapy. However, little is known about the mechanisms through which ATG4B deprivation suppresses the growth of cancer cells. METHODS: Cancer cells were transfected with either siRNA against ATG4B or an expression vector encoding wild-type ATG4BWT or encoding catalytic mutant ATG4BC74A to determine cell cycle progression by propidium iodide staining or by BrdU incorporation assay using flow cytometry...
November 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29153408/ampk-sensing-glucose-as-well-as-cellular-energy-status
#20
REVIEW
Sheng-Cai Lin, D Grahame Hardie
Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation...
November 15, 2017: Cell Metabolism
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