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Cell Death & Disease

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https://www.readbyqxmd.com/read/29449668/rhinovirus-3c-protease-suppresses-apoptosis-and-triggers-caspase-independent-cell-death
#1
Mark Lötzerich, Pascal S Roulin, Karin Boucke, Robert Witte, Oleg Georgiev, Urs F Greber
Apoptosis and programmed necrosis (necroptosis) determine cell fate, and antagonize infection. Execution of these complementary death pathways involves the formation of receptor-interacting protein kinase 1 (RIPK1) containing complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor-domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated-protein with death domain), NEMO (NF-κB regulatory subunit IKKγ), SQSTM1 (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are involved in RNA sensing, NF-κB signaling, autophagosome formation, apoptosis, and necroptosis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449653/cftr-mutation-enhances-dishevelled-degradation-and-results-in-impairment-of-wnt-dependent-hematopoiesis
#2
Huaqin Sun, Yan Wang, Jieting Zhang, Yan Chen, Yanyan Liu, Ziyuan Lin, Mingfeng Liu, Kai Sheng, Huijuan Liao, Kam Sze Tsang, Xiaohu Zhang, Xiaohua Jiang, Wenming Xu, Meng Mao, Hsiao Chang Chan
Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) with a multitude of clinical manifestations. Some CF patients develop clinically significant anemia, suggesting that CFTR may regulate hematopoiesis. Here, we report that cftr mutant zebrafish model exhibits primitive and definitive hematopoietic defects with impaired Wnt signaling. Cftr is found to interact, via its PDZ-binding domain (PDZBD), with Dishevelled (Dvl), a key component of Wnt signaling required for hematopoietic progenitor specification, thus protecting Dvl from Dapper1 (Dpr1)-induced lysosomal degradation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449647/the-pro-inflammatory-phenotype-of-the-human-non-classical-monocyte-subset-is-attributed-to-senescence
#3
Siew-Min Ong, Eva Hadadi, Truong-Minh Dang, Wei-Hseun Yeap, Crystal Tze-Ying Tan, Tze-Pin Ng, Anis Larbi, Siew-Cheng Wong
Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14 high /CD16 - ), intermediate (CD14 high /CD16 + ), and non-classical (CD14 low /CD16 + ). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro, yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#4
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449642/nit1-suppresses-tumour-proliferation-by-activating-the-tgf%C3%AE-1-smad2-3-signalling-pathway-in-colorectal-cancer
#5
Chun Lin, Jianming Zhang, Yanxia Lu, Xiaomin Li, Wenjuan Zhang, Wei Zhang, Weihao Lin, Lin Zheng, Xuenong Li
NIT1 protein has been reported to be a potential tumour suppressor in tumour progression. However, little is known about the specific role of NIT1 in tumour development and progression. In this study, we confirmed the specific effects of NIT1 in the regulation of colorectal carcinoma cell proliferation. Here, we showed that NIT1 was significantly downregulated in colorectal cancer tissues compared with that in adjacent normal tissues. The decreased expression of NIT1 was significantly correlated with poor differentiation and more serosal invasion...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449625/toll-like-receptor-4-modulation-influences-human-neural-stem-cell-proliferation-and-differentiation
#6
Chiara Grasselli, Daniela Ferrari, Cristina Zalfa, Matias Soncini, Gianluigi Mazzoccoli, Fabio A Facchini, Laura Marongiu, Francesca Granucci, Massimiliano Copetti, Angelo Luigi Vescovi, Francesco Peri, Lidia De Filippis
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449600/glucocorticoids-promote-apoptosis-of-proinflammatory-monocytes-by-inhibiting-erk-activity
#7
Adrian Achuthan, Ahmad S M Aslam, Quyen Nguyen, Pui-Yeng Lam, Andrew J Fleetwood, Ashlee T Frye, Cynthia Louis, Ming-Chin Lee, Julia E Smith, Andrew D Cook, Moshe Olshansky, Stephen J Turner, John A Hamilton
Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is complex and still debatable. One likely cellular target of GCs are monocytes/macrophages. The role of GCs in monocyte survival is also debated. Although both granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) are important regulators of macrophage lineage functions including their survival, the former is often associated with proinflammatory functions while the latter is important in lineage homeostasis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449593/hemopexin-is-required-for-adult-neurogenesis-in-the-subventricular-zone-olfactory-bulb-pathway
#8
Yanling Zhu, Yang Qiu, Mengjia Chen, Yi Zhang, Li Cao, Zhida Su, Yimin Yuan, Aijun Huang, Yinyan Pu, Cheng He
The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449584/crispr-whole-genome-screening-identifies-new-necroptosis-regulators-and-ripk1-alternative-splicing
#9
Marinella G Callow, Colin Watanabe, Katherine E Wickliffe, Russell Bainer, Sarah Kummerfield, Julie Weng, Trinna Cuellar, Vasantharajan Janakiraman, Honglin Chen, Ben Chih, Yuxin Liang, Benjamin Haley, Kim Newton, Michael R Costa
The necroptotic cell death pathway is a key component of human pathogen defense that can become aberrantly derepressed during tissue homeostasis to contribute to multiple types of tissue damage and disease. While formation of the necrosome kinase signaling complex containing RIPK1, RIPK3, and MLKL has been extensively characterized, additional mechanisms of its regulation and effector functions likely remain to be discovered. We screened 19,883 mouse protein-coding genes by CRISPR/Cas9-mediated gene knockout for resistance to cytokine-induced necroptosis and identified 112 regulators and mediators of necroptosis, including 59 new candidate pathway components with minimal or no effect on cell growth in the absence of necroptosis induction...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#10
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca 2+ concentration and the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449562/chir99021-and-valproic-acid-reduce-the-proliferative-advantage-of-apc-mutant-cells
#11
Alistair J Langlands, Thomas D Carroll, Yu Chen, Inke Näthke
More than 90% of colorectal cancers carry mutations in Apc that drive tumourigenesis. A 'just-right' signalling model proposes that Apc mutations stimulate optimal, but not excessive Wnt signalling, resulting in a growth advantage of Apc mutant over wild-type cells. Reversal of this growth advantage constitutes a potential therapeutic approach. We utilised intestinal organoids to compare the growth of Apc mutant and wild-type cells. Organoids derived from Apc Min/+ mice recapitulate stages of intestinal polyposis in culture...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449560/knockout-of-zebrafish-interleukin-7-receptor-il7r-by-the-crispr-cas9-system-delays-retinal-neurodevelopment
#12
Shijiao Cai, Yang Chen, Yue Shang, Jianlin Cui, Zongjin Li, Yuhao Li
Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449559/downregulation-of-srebp-inhibits-tumor-growth-and-initiation-by-altering-cellular-metabolism-in-colon-cancer
#13
Yang-An Wen, Xiaopeng Xiong, Yekaterina Y Zaytseva, Dana L Napier, Emma Vallee, Austin T Li, Chi Wang, Heidi L Weiss, B Mark Evers, Tianyan Gao
Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#14
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449553/nuclear-factor-90-promotes-angiogenesis-by-regulating-hif-1%C3%AE-vegf-a-expression-through-the-pi3k-akt-signaling-pathway-in-human-cervical-cancer
#15
Wenqian Zhang, Zhengai Xiong, Tianqin Wei, Qiumeng Li, Ying Tan, Li Ling, Xiushan Feng
Vascular endothelial growth factor A (VEGF-A), a fundamental component of angiogenesis, provides nutrients and oxygen to solid tumors, and enhances tumor cell survival, invasion, and migration. Nuclear factor 90 (NF90), a double-stranded RNA-binding protein, is strongly expressed in several human cancers, promotes tumor growth by reducing apoptosis, and increasing cell cycle process. The mechanisms by which cervical cancer cells inducing VEGF-A expression and angiogenesis upon NF90 upregulation remain to be fully established...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449550/meeting-report-the-8th-barossa-meeting-cell-signaling-in-cancer-medicine-in-the-barossa-valley-australia
#16
Guillermo A Gomez, Joanna M Woodcock, Vinay Tergaonkar, Philip A Gregory
No abstract text is available yet for this article.
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449545/transcriptional-repression-of-dna-repair-genes-is-a-hallmark-and-a-cause-of-cellular-senescence
#17
Guillaume Collin, Anda Huna, Marine Warnier, Jean-Michel Flaman, David Bernard
Cellular senescence response is (i) activated by numerous stresses, (ii) is characterized by a stable proliferation arrest, and (iii) by a set of specific features. Timely regulated senescence is thought to be beneficial, whereas chronic senescence such as during normal or premature aging is deleterious as it favors most, if not all, age-related diseases. In this study, using in-house or publicly available microarray analyses of transcriptomes of senescent cells, as well as analyses of the level of expression of several DNA repair genes by RT-qPCR and immunoblot, we show that repression of DNA repair gene expression is associated with cellular senescence...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449544/peak1-acting-as-a-tumor-promoter-in-colorectal-cancer-is-regulated-by-the-egfr-kras-signaling-axis-and-mir-181d
#18
Lanlan Huang, Chuangyu Wen, Xiangling Yang, Qiong Lou, Xiaoyan Wang, Jia Che, Junxiong Chen, Zihuan Yang, Xiaojian Wu, Meijin Huang, Ping Lan, Lei Wang, Aikichi Iwamoto, Jianping Wang, Huanliang Liu
PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis, but little is known about the role of PEAK1 in colorectal cancer (CRC) progression. We investigated the expression pattern, function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is overexpressed in CRC tissues and that high PEAK1 expression predicts poor survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1 inhibits cell proliferation, migration, and invasion in vitro and inhibits the growth of tumor xenografts in nude mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449542/long-non-coding-rnas-in-ischemic-stroke
#19
REVIEW
Mei-Hua Bao, Vivian Szeto, Burton B Yang, Shu-Zhen Zhu, Hong-Shuo Sun, Zhong-Ping Feng
Stroke is one of the leading causes of mortality and disability worldwide. Uncovering the cellular and molecular pathophysiological processes in stroke have been a top priority. Long non-coding (lnc) RNAs play critical roles in different kinds of diseases. In recent years, a bulk of aberrantly expressed lncRNAs have been screened out in ischemic stroke patients or ischemia insulted animals using new technologies such as RNA-seq, deep sequencing, and microarrays. Nine specific lncRNAs, antisense non-coding RNA in the INK4 locus (ANRIL), metastasis-associate lung adenocarcinoma transcript 1 (MALAT1), N1LR, maternally expressed gene 3 (MEG3), H19, CaMK2D-associated transcript 1 (C2dat1), Fos downstream transcript (FosDT), small nucleolar RNA host gene 14 (SNHG14), and taurine-upregulated gene 1 (TUG1), were found increased in cerebral ischemic animals and/or oxygen-glucose deprived (OGD) cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449541/long-noncoding-rna-meg3-suppresses-liver-cancer-cells-growth-through-inhibiting-%C3%AE-catenin-by-activating-pkm2-and-inactivating-pten
#20
Qidi Zheng, Zhuojia Lin, Jie Xu, Yanan Lu, Qiuyu Meng, Chen Wang, Yuxin Yang, Xiaoru Xin, Xiaonan Li, Hu Pu, Xin Gui, Tianming Li, Wujun Xiong, Dongdong Lu
Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor and has been showed to involve in a variety of cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3 promotes the expression and maturition of miR122 which targets PKM2. Therefore, MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122. Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer cells...
February 15, 2018: Cell Death & Disease
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