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Science Signaling

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https://www.readbyqxmd.com/read/28811384/loss-of-spdef-and-gain-of-tgfbi-activity-after-androgen-deprivation-therapy-promote-emt-and-bone-metastasis-of-prostate-cancer
#1
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811383/interleukin-36-cytokines-may-overcome-microbial-immune-evasion-strategies-that-inhibit-interleukin-1-family-signaling
#2
REVIEW
Liselotte E Jensen
Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811382/an-engineered-s1p-chaperone-attenuates-hypertension-and-ischemic-injury
#3
Steven L Swendeman, Yuquan Xiong, Anna Cantalupo, Hui Yuan, Nathalie Burg, Yu Hisano, Andreane Cartier, Catherine H Liu, Eric Engelbrecht, Victoria Blaho, Yi Zhang, Keisuke Yanagida, Sylvain Galvani, Hideru Obinata, Jane E Salmon, Teresa Sanchez, Annarita Di Lorenzo, Timothy Hla
Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM(+)HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28790197/breast-tumors-educate-the-proteome-of-stromal-tissue-in-an-individualized-but-coordinated-manner
#4
Xuya Wang, Arshag D Mooradian, Petra Erdmann-Gilmore, Qiang Zhang, Rosa Viner, Sherri R Davies, Kuan-Lin Huang, Ryan Bomgarden, Brian A Van Tine, Jieya Shao, Li Ding, Shunqiang Li, Matthew J Ellis, John C Rogers, R Reid Townsend, David Fenyö, Jason M Held
Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma in mice while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled by species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with 35% of the stromal proteome altered by tumors consistently across different animals and passages...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28790196/trif-dependent-toll-like-receptor-signaling-suppresses-scd1-transcription-in-hepatocytes-and-prevents-diet-induced-hepatic-steatosis
#5
Jing Chen, Jin Li, Jensen H C Yiu, Jenny K W Lam, Chi-Ming Wong, Bernhard Dorweiler, Aimin Xu, Connie W Woo
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28790195/the-tyrosine-phosphatase-shp-1-promotes-t-cell-adhesion-by-activating-the-adaptor-protein-crkii-in-the-immunological-synapse
#6
Inbar Azoulay-Alfaguter, Marianne Strazza, Michael Peled, Hila K Novak, James Muller, Michael L Dustin, Adam Mor
The adaptor protein CrkII regulates T cell adhesion by recruiting the guanine nucleotide exchange factor C3G, an activator of Rap1. Subsequently, Rap1 stimulates the integrin LFA-1, which leads to T cell adhesion and interaction with antigen-presenting cells (APCs). The adhesion of T cells to APCs is critical for their proper function and education. The interface between the T cell and the APC is known as the immunological synapse. It is characterized by the specific organization of proteins that can be divided into central supramolecular activation clusters (c-SMACs) and peripheral SMACs (p-SMACs)...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28765513/high-glucose-induced-ros-activates-trpm2-to-trigger-lysosomal-membrane-permeabilization-and-zn-2-mediated-mitochondrial-fission
#7
Nada Abuarab, Tim S Munsey, Lin-Hua Jiang, Jing Li, Asipu Sivaprasadarao
Diabetic stress increases the production of reactive oxygen species (ROS), leading to mitochondrial fragmentation and dysfunction. We hypothesized that ROS-sensitive TRPM2 channels mediated diabetic stress-induced mitochondrial fragmentation. We found that chemical inhibitors, RNAi silencing, and genetic knockout of TRPM2 channels abolished the ability of high glucose to cause mitochondrial fission in endothelial cells, a cell type that is particularly vulnerable to diabetic stress. Similar to high glucose, increasing ROS in endothelial cells by applying H2O2 induced mitochondrial fission...
August 1, 2017: Science Signaling
https://www.readbyqxmd.com/read/28765512/a-cluster-of-immunoresolvents-links-coagulation-to-innate-host-defense-in-human-blood
#8
Paul C Norris, Stephania Libreros, Nan Chiang, Charles N Serhan
Blood coagulation is a protective response that prevents excessive bleeding upon blood vessel injury. We investigated the relationship between coagulation and the resolution of inflammation and infection by lipid mediators (LMs) through metabololipidomics-based profiling of human whole blood (WB) during coagulation. We identified temporal clusters of endogenously produced prothrombotic and proinflammatory LMs (eicosanoids), as well as specialized proresolving mediators (SPMs). In addition to eicosanoids, a specific SPM cluster was identified that consisted of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B4, and maresin 1, each of which was present at bioactive concentrations (0...
August 1, 2017: Science Signaling
https://www.readbyqxmd.com/read/28743803/the-glucocorticoid-angptl4-ceramide-axis-induces-insulin-resistance-through-pp2a-and-pkc%C3%AE
#9
Tzu-Chieh Chen, Daniel I Benjamin, Taiyi Kuo, Rebecca A Lee, Mei-Lan Li, Darryl J Mar, Damian E Costello, Daniel K Nomura, Jen-Chywan Wang
Chronic glucocorticoid exposure is associated with the development of insulin resistance. We showed that glucocorticoid-induced insulin resistance was attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced lipolysis in white adipose tissue. Through metabolomic profiling, we revealed that glucocorticoid treatment increased hepatic ceramide concentrations by inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent manner...
July 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28743802/enhancing-natriuretic-peptide-signaling-in-adipose-tissue-but-not-in-muscle-protects-against-diet-induced-obesity-and-insulin-resistance
#10
Wei Wu, Fubiao Shi, Dianxin Liu, Ryan P Ceddia, Robert Gaffin, Wan Wei, Huafeng Fang, E Douglas Lewandowski, Sheila Collins
In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can stimulate lipolysis in adipocytes and promote the "browning" of white adipose tissue. NPs may also increase the oxidative capacity of skeletal muscle. To unravel the contribution of NP-stimulated metabolism in adipose tissue compared to that in muscle in vivo, we generated mice with tissue-specific deletion of the NP clearance receptor, NPRC, in adipose tissue (Nprc(AKO) ) or in skeletal muscle (Nprc(MKO) ). We showed that, similar to Nprc null mice, Nprc(AKO) mice, but not Nprc(MKO) mice, were resistant to obesity induced by a high-fat diet...
July 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#11
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#12
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720716/pi3k%C3%AE-activity-in-leukocytes-promotes-adipose-tissue-inflammation-and-early-onset-insulin-resistance-during-obesity
#13
Ludovic Breasson, Barbara Becattini, Claudia Sardi, Angela Molinaro, Fabio Zani, Romina Marone, Fabrizio Botindari, Mélanie Bousquenaud, Curzio Ruegg, Matthias P Wymann, Giovanni Solinas
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet-induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698220/activation-of-camkiv-by-soluble-amyloid-%C3%AE-1-42-impedes-trafficking-of-axonal-vesicles-and-impairs-activity-dependent-synaptogenesis
#14
Daehun Park, Myeongsu Na, Jung Ah Kim, Unghwi Lee, Eunji Cho, Mirye Jang, Sunghoe Chang
The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. We found that sAβ1-42 prevented new synapse formation induced by chemical long-term potentiation (cLTP). In cultured rat hippocampal neurons, nanomolar amounts of sAβ1-42 impaired Ca(2+) clearance from presynaptic terminals and increased the basal Ca(2+) concentration...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#15
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698218/heart-failure-inhibitor
#16
John F Foley
Targeting a G protein-coupled receptor in cardiomyocytes offers protection in a mouse model of cardiac failure.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698217/new-connections-amyloid-%C3%AE-calcium-and-the-synapse
#17
Leslie K Ferrarelli
Insight into how amyloid-β impairs synaptic function reveals potential therapeutic targets for patients with Alzheimer's disease.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698216/paper-of-note-in-science-translational-medicine9-397
#18
Leslie K Ferrarelli
This week's article describes how chemotherapy unintentionally enhances the dissemination of cancer cells into the circulation.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698215/paper-of-note-in-science357-6346
#19
Annalisa M VanHook
This week's article offers a possible explanation for how Zika virus causes microcephaly.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#20
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
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