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https://www.readbyqxmd.com/read/29603367/frontline-science-il-18-primes-murine-nk-cells-for-proliferation-by-promoting-protein-synthesis-survival-and-autophagy
#1
Yosif El-Darawish, Wen Li, Kyosuke Yamanishi, Magdalena Pencheva, Naoto Oka, Hiromichi Yamanishi, Tomohiro Matsuyama, Yoshimasa Tanaka, Nagahiro Minato, Haruki Okamura
Combined stimulation by IL-2 and IL-18 effectively promotes proliferation of NK cells, whereas singular stimulation does not. In this study, synergistic effects of these cytokines on NK cells proliferation was analyzed, focusing on the roles of IL-18. In splenic resting NK cells from IL-18KO mice, IL-18 rapidly activated NF-κB independently of IL-2, and activated or up-regulated various molecules downstream of PI3K/AKT and mTOR, including S6, Bcl-XL, ATG5, and LC3II, accompanying increases in cell growth and survival...
March 30, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29598951/overexpression-of-pik3ca-in-head-and-neck-squamous-cell-carcinoma-is-associated-with-poor-outcome-and-activation-of-the-yap-pathway
#2
Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M Paramio, Corina Lorz
OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved...
April 2018: Oral Oncology
https://www.readbyqxmd.com/read/29587825/inflammatory-interferon-activates-hif-1%C3%AE-mediated-epithelial-to-mesenchymal-transition-via-pi3k-akt-mtor-pathway
#3
Yen-Hsiu Yeh, Ho-Fu Hsiao, Yen-Cheng Yeh, Tien-Wen Chen, Tsai-Kun Li
BACKGROUND: Tumor microenvironments (TMEs) activate various axes/pathways, predominantly inflammatory and hypoxic responses, impact tumorigenesis, metastasis and therapeutic resistance significantly. Although molecular pathways of individual TME are extensively studied, evidence showing interaction and crosstalk between hypoxia and inflammation remain unclear. Thus, we examined whether interferon (IFN) could modulate both inflammatory and hypoxic responses under normoxia and its relation with cancer development...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29578532/critical-role-of-ox40-signaling-in-the-tcr-independent-phase-of-human-and-murine-thymic-treg-generation
#4
Prabhakaran Kumar, Alejandra Marinelarena, Divya Raghunathan, Vandhana K Ragothaman, Shikha Saini, Palash Bhattacharya, Jilao Fan, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of Treg function can lead to the development of autoimmunity. Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery, where they suppress self-reactive effector T cells (Teff) responses. Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation (CAP-independent) in the presence of low-dose IL-2. Therefore, we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg (tTreg) development...
March 26, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29578162/the-autophagy-induced-by-curcumin-via-mek-erk-pathway-plays-an-early-anti-leukemia-role-in-human-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-sup-b15-cells
#5
Yong Guo, Qing Qing Shan, Ping Yu Gong, Sen Chun Wang
Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph+ ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph+ ALL...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29518979/metabolic-reprogramming-and-the-recovery-of-physiological-functionality-in-3d-cultures-in-micro-bioreactors
#6
Krzysztof Wrzesinski, Stephen J Fey
The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed...
March 7, 2018: Bioengineering
https://www.readbyqxmd.com/read/29516642/inpp4b-restrains-cell-proliferation-and-metastasis-via-regulation-of-the-pi3k-akt-sgk-pathway
#7
Ying Chen, Zeyu Sun, Mei Qi, Xiao Wang, Weifang Zhang, Chunyan Chen, Juan Liu, Weiming Zhao
Cervical cancer continues to be among the most frequent gynaecologic cancers worldwide. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway is constitutively activated in cervical cancer. Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway. INPP4B has diverse roles in various tumours, but its role in cervical cancer is largely unknown. In this study, we investigated the role of INPP4B in cervical cancer...
March 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29492195/peroxiredoxin-1-promotes-cell-proliferation-and-metastasis-through-enhancing-akt-mtor-in-human-osteosarcoma-cells
#8
An-Lie Cai, Wei Zeng, Wei-Liang Cai, Jing-Ling Liu, Xue-Wen Zheng, Ying Liu, Xiang-Cheng Yang, Yi Long, Jie Li
Osteosarcoma is characterized by high propensity for metastasis, especially to the lung, which is the main cause of death. Peroxiredoxin-1 (PRDX1) plays significant roles in multiple processes of initiation and progression of tumorogenesis. However, whether PRDX1 participates in metastasis of osteosarcoma remains unknown. Here, we demonstrate that PRDX1 overexpressed in osteosarcoma tissues comparing to adjacent non-tumor tissues. Two independent cohorts of patients showed high level of PRDX1 correlated with clinicopathological features such as larger tumor size and advanced tumor metastasis stage...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29463194/the-expression-and-prognostic-impact-of-the-pi3k-akt-mtor-signaling-pathway-in-advanced-esophageal-squamous-cell-carcinoma
#9
Ning Wu, Zunguo Du, Yongjun Zhu, Yang Song, Liewen Pang, Zhiming Chen
The abnormal phosphatase and tensin homolog expression and activated phosphoinositide-3 kinase/Protein kinase B (AKT)/mammalian target of rapamycin signaling pathway are involved in the progression of esophageal squamous cell carcinoma. By assessing the expression pattern of key components in the phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway by immunohistochemistry in tumor and nontumor esophageal mucosa from patients with esophageal squamous cell carcinomas, we aimed to carefully explore the relationship between the various protein expressions and clinicopathological factors, as well as patient outcome...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29462661/p66shc-regulates-migration-of-castration-resistant-prostate-cancer-cells
#10
Matthew A Ingersoll, Yu-Wei Chou, Jamie S Lin, Ta-Chun Yuan, Dannah Miller, Yan Xie, Yaping Tu, Rebecca E Oberley-Deegan, Surinder K Batra, Ming-Fong Lin
Metastatic castration-resistant (CR) prostate cancer (PCa) is a lethal disease for which no effective treatment is currently available. p66Shc is an oxidase previously shown to promote androgen-independent cell growth through generation of reactive oxygen species (ROS) and elevated in clinical PCa and multiple CR PCa cell lines. We hypothesize p66Shc also increases the migratory activity of PCa cells through ROS and investigate the associated mechanism. Using the transwell assay, our study reveals that the level of p66Shc protein correlates with cell migratory ability across several PCa cell lines...
February 17, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29461205/pten-negatively-regulates-the-cell-lineage-progression-from-ng2-glial-progenitor-to-oligodendrocyte-via-mtor-independent-signaling
#11
Estibaliz González-Fernández, Hey-Kyeong Jeong, Masahiro Fukaya, Hyukmin Kim, Rabia R Khawaja, Isha N Srivastava, Ari Waisman, Young-Jin Son, Shin H Kang
Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the primary players for OL regeneration, targetable OPC-specific intracellular signaling mechanisms for facilitated OL regeneration remain elusive. Here, we report that OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific manipulations, markedly promotes OL differentiation and regeneration in the mature CNS...
February 20, 2018: ELife
https://www.readbyqxmd.com/read/29460925/clinical-implications-of-pten-loss-in-prostate-cancer
#12
REVIEW
Tamara Jamaspishvili, David M Berman, Ashley E Ross, Howard I Scher, Angelo M De Marzo, Jeremy A Squire, Tamara L Lotan
Genomic aberrations of the PTEN tumour suppressor gene are among the most common in prostate cancer. Inactivation of PTEN by deletion or mutation is identified in ∼20% of primary prostate tumour samples at radical prostatectomy and in as many as 50% of castration-resistant tumours. Loss of phosphatase and tensin homologue (PTEN) function leads to activation of the PI3K-AKT (phosphoinositide 3-kinase-RAC-alpha serine/threonine-protein kinase) pathway and is strongly associated with adverse oncological outcomes, making PTEN a potentially useful genomic marker to distinguish indolent from aggressive disease in patients with clinically localized tumours...
April 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29454321/safety-and-efficacy-of-temsirolimus-as-second-line-treatment-for-patients-with-recurrent-bladder-cancer
#13
Marina Pulido, Guilhem Roubaud, Anne-Laure Cazeau, Hakim Mahammedi, Lionel Vedrine, Florence Joly, Loic Mourey, Christian Pfister, Alejandro Goberna, Barbara Lortal, Carine Bellera, Philippe Pourquier, Nadine Houédé
BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#14
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29443546/akt1-deficiency-diminishes-skeletal-muscle-hypertrophy-by-reducing-satellite-cell-proliferation
#15
Nobuki Moriya, Mitsunori Miyazaki
Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29428729/downregulated-cdkn1c-p57kip2-drives-tumorigenesis-and-associates-with-poor-overall-survival-in-breast-cancer
#16
Zhu Qiu, Yunhai Li, Beilei Zeng, Xiaoqin Guan, Hongzhong Li
CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29416002/ezh2-inhibits-autophagic-cell-death-of-aortic-vascular-smooth-muscle-cells-to-affect-aortic-dissection
#17
Rui Li, Xin Yi, Xiang Wei, Bo Huo, Xian Guo, Cai Cheng, Ze-Min Fang, Jing Wang, Xin Feng, Ping Zheng, Yun-Shu Su, Jackson Ferdinand Masau, Xue-Hai Zhu, Ding-Sheng Jiang
Enhancer of zeste homolog 2 (EZH2), a methyltransferase that di- and tri-methylates lysine-27 of histone H3, largely functions as a transcriptional repressor, and plays a critical role in various kinds of cancers. Here we report a novel function of EZH2 in regulating autophagic cell death (ACD) of vascular smooth muscle cells (VSMCs) that affect aortic dissection (AD). Inhibition of EZH2 activity by UNC1999 or knockdown EZH2 resulted in VSMC loss, while overexpression of EZH2 facilitated VSMC growth, and these effects of EZH2 on VSMCs were independent of proliferation and apoptosis...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29398519/compound-c-enhances-tau-phosphorylation-at-serine396-via-pi3k-activation-in-an-ampk-and-rapamycin-independent-way-in-differentiated-sh-sy5y-cells
#18
Shohreh Majd, Simon Koblar, John Power
Aggregation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFT) is a main hallmark for Alzheimer's disease (AD). Activation of cellular metabolic axis, made of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) have been implicated in generating tau pathology of AD. Thus, blocking either of these two proteins or both, are suggested as the future therapeutic approaches for AD. How and to what level these approaches could be applied, however are not entirely clear...
January 31, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29386088/phosphoglycerate-mutase-1-pgam1-promotes-pancreatic-ductal-adenocarcinoma-pdac-metastasis-by-acting-as-a-novel-downstream-target-of-pi3k-akt-mtor-pathway
#19
Xinlu Liu, Xiaodong Tan, Peng Liu, Yunhao Wu, Songying Qian, Xiaobo Zhang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors known, with an overall 5-year survival rate of less than 6% due to early local invasion and distant metastasis. Exploring suitable therapeutic targets associated with invasion and metastasis is required for improving the prognosis of PDAC. In this study, we investigated the role of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) in PDAC. PGAM1 expression was examined in tissue samples of 54 PDAC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined...
January 31, 2018: Oncology Research
https://www.readbyqxmd.com/read/29384220/compound-c-induces-protective-autophagy-in-human-cholangiocarcinoma-cells-via-akt-mtor-independent-pathway
#20
Xiaofang Zhao, Guosong Luo, Ying Cheng, Wenjing Yu, Run Chen, Bin Xiao, Yuancai Xiang, Chunhong Feng, Wenguang Fu, Chunyan Duan, Fuli Yao, Xianming Xia, Qinghua Tao, Mei Wei, Rongyang Dai
Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to exert antitumor activities in some types of cells. Whether compound C can exert antitumor effects in human cholangiocarcinoma (CCA) remains unknown. Here, we demonstrated that compound C is a potent inducer of cell death and autophagy in human CCA cells. Autophagy inhibitors increased the cytotoxicity of compound C towards human CCA cells, as confirmed by increased LDH release and PARP cleavage. It is notable that compound C treatment increased phosphorylated Akt, sustained high levels of phosphorylated p70S6K and decreased mTOR regulated p-ULK1 (ser757)...
January 31, 2018: Journal of Cellular Biochemistry
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