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Cell Death and Differentiation

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https://www.readbyqxmd.com/read/28731466/interaction-of-galectin-3-with-muc1-on-cell-surface-promotes-egfr-dimerization-and-activation-in-human-epithelial-cancer-cells
#1
Tushar Piyush, Anisha R Chacko, Paulina Sindrewicz, John Hilkens, Jonathan M Rhodes, Lu-Gang Yu
Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28731465/pr-set7-deficiency-limits-uterine-epithelial-population-growth-hampering-postnatal-gland-formation-in-mice
#2
Tongtong Cui, Bo He, Shuangbo Kong, Chan Zhou, Hangxiao Zhang, Zhangli Ni, Haili Bao, Jingtao Qiu, Qiliang Xin, Danny Reinberg, John P Lydon, Jinhua Lu, Haibin Wang
Formation of secretary endometrial glands in the uterus known as adenogenesis is a typical process of branching morphogenesis involving dynamic epithelial growth and differentiation. Unsuccessful adenogenesis often leads to female infertility. However, it remains largely unexplored so far regarding the epigenetic machinery governing normal endometrial gland formation. Here, we demonstrated that PR-Set7, an epigenetic regulator for H4K20me1 modification, was extensively expressed in the postnatal uteri, and its conditional deletion resulted in a complete lack of endometrial glands and infertility in mice...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28731464/trophoblast-survival-signaling-during-human-placentation-requires-hsp70-activation-of-mmp2-mediated-hbegf-shedding
#3
Chandni V Jain, Philip Jessmon, Charbel T Barrak, Alan D Bolnick, Brian A Kilburn, Michael Hertz, D Randall Armant
Survival of trophoblast cells in the low oxygen environment of human placentation requires metalloproteinase-mediated shedding of HBEGF and downstream signaling. A matrix metalloproteinase (MMP) antibody array and quantitative RT-PCR revealed upregulation of MMP2 post-transcriptionally in human first trimester HTR-8/SVneo trophoblast cells and placental villous explants exposed to 2% O2. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. Because α-amanitin inhibited the upregulation of HBEGF, differentially expressed genes were identified by next-generation sequencing of RNA from trophoblast cells cultured at 2% O2 for 0, 1, 2 and 4 h...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28731463/peroxisomes-protect-lymphoma-cells-from-hdac-inhibitor-mediated-apoptosis
#4
Michael S Dahabieh, ZongYi Ha, Erminia Di Pietro, Jessica N Nichol, Alicia M Bolt, Christophe Goncalves, Daphné Dupéré-Richer, Filippa Pettersson, Koren K Mann, Nancy E Braverman, Sonia V Del Rincón, Wilson H Miller
Peroxisomes are a critical rheostat of reactive oxygen species (ROS), yet their role in drug sensitivity and resistance remains unexplored. Gene expression analysis of clinical lymphoma samples suggests that peroxisomes are involved in mediating drug resistance to the histone deacetylase inhibitor (HDACi) Vorinostat (Vor), which promotes ROS-mediated apoptosis. Vor augments peroxisome numbers in cultured lymphoma cells, concomitant with increased levels of peroxisomal proteins PEX3, PEX11B, and PMP70. Genetic inhibition of peroxisomes, using PEX3 knockdown, reveals that peroxisomes protect lymphoma cells against Vor-mediated cell death...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#5
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28708137/fas-apoptotic-inhibitory-molecule-2-is-a-stress-induced-intrinsic-neuroprotective-factor-in-the-retina
#6
Mercy Pawar, Boris Busov, Aaruran Chandrasekhar, Jingyu Yao, David N Zacks, Cagri G Besirli
We report the neuroprotective role of FAS apoptotic inhibitory molecule 2 (FAIM2), an inhibitor of the FAS signaling pathway, during stress-induced photoreceptor apoptosis. Retinal detachment resulted in increased FAIM2 levels in photoreceptors with higher amounts detected at the tips of outer segments. Activation of FAS death receptor via FAS-ligand led to JNK-mediated FAIM2 phosphorylation, decreased proteasome-mediated degradation and increased association with the FAS receptor. Photoreceptor apoptosis was accelerated in Faim2 knockout mice following experimental retinal detachment...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28708136/differential-requirements-for-tousled-like-kinases-1-and-2-in-mammalian-development
#7
Sandra Segura-Bayona, Philip A Knobel, Helena González-Burón, Sameh A Youssef, Aida Peña-Blanco, Étienne Coyaud, Teresa López-Rovira, Katrin Rein, Lluís Palenzuela, Julien Colombelli, Stephen Forrow, Brian Raught, Anja Groth, Alain de Bruin, Travis H Stracker
The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28708135/regulation-of-plk1-through-competition-between-hnrnpk-mir-149-3p-and-mir-193b-5p
#8
Chang Hoon Shin, Hong Lee, Hye Ree Kim, Kyung Hee Choi, Je-Gun Joung, Hyeon Ho Kim
Polo-like kinase 1 (PLK1) is a critical regulator of cell cycle progression and apoptosis. However, its regulation remains poorly understood. In the present study, we investigated the molecular mechanism underlying the post-transcriptional regulation of PLK1. We observed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) and PLK1 were positively associated in several different cancers and high expression levels of them correlated with poor prognosis in patients with cancer. Knockdown of hnRNPK resulted in reduced expression of PLK1, whereas conversely, PLK1 expression was increased in hnRNPK-overexpressing cells...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28686580/upregulation-of-lyar-induces-neuroblastoma-cell-proliferation-and-survival
#9
Yuting Sun, Bernard Atmadibrata, Denise Yu, Matthew Wong, Bing Liu, Nicholas Ho, Dora Ling, Andrew E Tee, Jenny Wang, Imran N Mungrue, Pei Y Liu, Tao Liu
The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28686579/synergy-between-prkdc-and-trp53-regulates-stem-cell-proliferation-and-gi-ars-after-irradiation
#10
Kay E Gurley, Amanda K Ashley, Russell D Moser, Christopher J Kemp
Ionizing radiation (IR) is one of the most widely used treatments for cancer. However, acute damage to the gastrointestinal tract or gastrointestinal acute radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the mechanisms that underlie this remain unclear. Here we use mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. IR induces DNA double strand breaks and DNA-PK mutant Prkdc(scid/scid) mice are sensitive to GI-ARS due to an inability to repair these breaks...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28686578/culling-of-apcs-by-inflammatory-cell-death-pathways-restricts-tim3-and-pd-1-expression-and-promotes-the-survival-of-primed-cd8-t-cells
#11
Rajen Patel, Kwangsin Kim, Bojan Shutinoski, Kristina Wachholz, Lakshmi Krishnan, Subash Sad
We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8(+) T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8(+) T cells. However, the maintenance of primed CD8(+) T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28686577/mtor-raptor-signaling-is-critical-for-skeletogenesis-in-mice-through-the-regulation-of-runx2-expression
#12
Qinggang Dai, Zhan Xu, Xuhui Ma, Ningning Niu, Siru Zhou, Furong Xie, Lingyong Jiang, Jun Wang, Weiguo Zou
The mammalian target of rapamycin (mTOR)/regulatory-associated protein of mTOR (Raptor) pathway transmits and integrates different signals including growth factors, nutrients, and energy metabolism. Nearly all these signals have been found to play roles in skeletal biology. However, the contribution of mTOR/Raptor to osteoblast biology in vivo remains to be elucidated as the conclusions of recent studies are controversial. Here we report that mice with a deficiency of either mTOR or Raptor in preosteoblasts exhibited clavicular hypoplasia and delayed fontanelle fusion, similar to those found in human patients with cleidocranial dysplasia (CCD) haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2) or those identified in Runx2(+/-) mice...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28665403/dram-3-modulates-autophagy-and-promotes-cell-survival-in-the-absence-of-glucose-open
#13
M Mrschtik, J O'Prey, L Y Lao, J S Long, F Beaumatin, D Strachan, M O'Prey, J Skommer, K M Ryan
This corrects the article DOI: 10.1038/cdd.2015.26.
June 30, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28665402/germline-bap1-mutations-induce-a-warburg-effect
#14
Angela Bononi, Haining Yang, Carlotta Giorgi, Simone Patergnani, Laura Pellegrini, Mingming Su, Guoxiang Xie, Valentina Signorato, Sandra Pastorino, Paul Morris, Greg Sakamoto, Shafi Kuchay, Giovanni Gaudino, Harvey I Pass, Andrea Napolitano, Paolo Pinton, Wei Jia, Michele Carbone
Carriers of heterozygous germline BAP1 mutations (BAP1(+/-)) develop cancer. We studied plasma from 16 BAP1(+/-) individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1(WT)) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1(WT) and BAP1(+/-) individuals...
June 30, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28665401/pd-l1-and-iaps-co-operate-to-protect-tumors-from-cytotoxic-lymphocyte-derived-tnf
#15
Conor J Kearney, Najoua Lalaoui, Andrew J Freeman, Kelly M Ramsbottom, John Silke, Jane Oliaro
Smac-mimetics are emerging as promising anti-cancer agents and are being evaluated in clinical trials for a variety of malignancies. Smac-mimetics can induce TNF production from a subset of tumor cells and simultaneously sensitize them to TNF-induced apoptosis. However, TNF derived from other cellular sources, such as cytotoxic lymphocytes (CLs) within the tumor, may also contribute to the anti-tumor activity of SMs. Here, we show that CD8(+) T cells and NK cells potently kill tumor cells in the presence of the SM, birinapant...
June 30, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644441/micrornas-143-and-145-induce-epithelial-to-mesenchymal-transition-and-modulate-the-expression-of-junction-proteins
#16
Lidia Avalle, Danny Incarnato, Aurora Savino, Marta Gai, Francesca Marino, Sara Pensa, Isaia Barbieri, Michael B Stadler, Paolo Provero, Salvatore Oliviero, Valeria Poli
Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma's metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644440/lncrna-sarcc-suppresses-renal-cell-carcinoma-rcc-progression-via-altering-the-androgen-receptor-ar-mirna-143-3p-signals
#17
Wei Zhai, Yin Sun, Changcheng Guo, Guanghui Hu, Mingchao Wang, Jiayi Zheng, WanYing Lin, Qingbo Huang, Gonghui Li, Junhua Zheng, Chawnshang Chang
While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644439/activation-of-cell-surface-grp78-decreases-endoplasmic-reticulum-stress-and-neuronal-death
#18
Morgane Louessard, Isabelle Bardou, Eloïse Lemarchand, Audrey M Thiebaut, Jérôme Parcq, Jérôme Leprince, Anne Terrisse, Valérie Carraro, Pierre Fafournoux, Alain Bruhat, Cyrille Orset, Denis Vivien, Carine Ali, Benoit D Roussel
The unfolded protein response (UPR) is an endoplasmic reticulum (ER) -related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644438/gut-check-dead-cell-samples-leads-to-tolerant-examples
#19
Thomas H Oguin, Jennifer Martinez
No abstract text is available yet for this article.
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#20
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
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