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https://www.readbyqxmd.com/read/28346462/wnt-tcf1-pathway-restricts-embryonic-stem-cell-cycle-through-activation-of-the-ink4-arf-locus
#1
Anchel De Jaime-Soguero, Francesco Aulicino, Gokhan Ertaylan, Anna Griego, Aniello Cerrato, Aravind Tallam, Antonio Del Sol, Maria Pia Cosma, Frederic Lluis
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346429/deletion-of-endothelial-cell-specific-liver-kinase-b1-increases-angiogenesis-and-tumor-growth-via-vascular-endothelial-growth-factor
#2
W Zhang, Y Ding, C Zhang, Q Lu, Z Liu, K Coughlan, I Okon, M-H Zou
Liver kinase B1 (LKB1) is a serine/threonine protein kinase ubiquitously expressed in mammalian cells. It was first identified in Peutz-Jeghers syndrome as a tumor suppressor gene. Whether endothelial LKB1 regulates angiogenesis and tumor growth is unknown. In this study, we generated endothelial cell-specific LKB1-knockout (LKB1(endo-/-)) mice by crossbreeding vascular endothelial-cadherin-Cre mice with LKB1(flox/flox) mice. Vascular endothelial growth factor (VEGF) level was highly co-stained in endothelial cells but not in macrophages in LKB1(endo-/-) mice...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346423/mob1-yap1-taz-nkx2-1-axis-controls-bronchioalveolar-cell-differentiation-adhesion-and-tumour-formation
#3
K Otsubo, H Goto, M Nishio, K Kawamura, S Yanagi, W Nishie, T Sasaki, T Maehama, H Nishina, K Mimori, T Nakano, H Shimizu, T W Mak, K Nakao, Y Nakanishi, A Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1a(flox/flox)/Mob1b(-/-); termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346422/the-metastatic-suppressor-ndrg1-inhibits-emt-migration-and-invasion-through-interaction-and-promotion-of-caveolin-1-ubiquitylation-in-human-colorectal-cancer-cells
#4
L Mi, F Zhu, X Yang, J Lu, Y Zheng, Q Zhao, X Wen, A Lu, M Wang, M Zheng, J Ji, J Sun
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346420/hepatic-cyclooxygenase-2-overexpression-induced-spontaneous-hepatocellular-carcinoma-formation-in-mice
#5
H Chen, W Cai, E S H Chu, J Tang, C-C Wong, S H Wong, W Sun, Q Liang, J Fang, Z Sun, J Yu
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#6
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345805/promoter-hypermethylation-mediated-downregulation-of-mir-770-and-its-host-gene-meg3-a-long-non-coding-rna-in-the-development-of-gastric-cardia-adenocarcinoma
#7
Wei Guo, Zhiming Dong, Shengnan Liu, Yiling Qiao, Gang Kuang, Yanli Guo, Supeng Shen, Jia Liang
Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes an lncRNA and is downregulated in an expanding list of cancer cell lines and primary human cancers. The miR-770 is transcribed from the intronic sequence of MEG3 and MEG3 may be the host gene for miR-770. However, the biological role of MEG3 and miR-770 in gastric cardia adenocarcinoma (GCA) development and prognosis is poorly defined. The present study was to investigate the function and methylation status of MEG3 in GCA, and further to detect the functional association of miR-770 and its host gene MEG3 in GCA carcinogenesis and prognosis...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345464/microrna-590-3p-promotes-cell-proliferation-and-invasion-by-targeting-inositol-polyphosphate-4-phosphatase-type-ii-in-human-prostate-cancer-cells
#8
Haiwen Chen, Qidong Luo, Hongliang Li
Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345455/recurrent-epigenetic-silencing-of-the-ptprd-tumor-suppressor-in-laryngeal-squamous-cell-carcinoma
#9
Marcin Szaumkessel, Sonia Wojciechowska, Joanna Janiszewska, Natalia Zemke, Ewa Byzia, Katarzyna Kiwerska, Magdalena Kostrzewska-Poczekaj, Adam Ustaszewski, Malgorzata Jarmuz-Szymczak, Reidar Grenman, Malgorzata Wierzbicka, Anna Bartochowska, Krzysztof Szyfter, Maciej Giefing
Cellular processes like differentiation, mitotic cycle, and cell growth are regulated by tyrosine kinases with known oncogenic potential and tyrosine phosphatases that downmodulate the first. Therefore, tyrosine phosphatases are recurrent targets of gene alterations in human carcinomas. We and others suggested recently a tumor suppressor function of the PTPRD tyrosine phosphatase and reported homozygous deletions of the PTPRD locus in laryngeal squamous cell carcinoma. In this study, we investigated other gene-inactivating mechanisms potentially targeting PTPRD, including loss-of-function mutations and also epigenetic alterations like promoter DNA hypermethylation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345453/tumor-suppressor-mir-29c-regulates-radioresistance-in-lung-cancer-cells
#10
Elena Arechaga-Ocampo, Cesar Lopez-Camarillo, Nicolas Villegas-Sepulveda, Claudia H Gonzalez-De la Rosa, Isidro X Perez-Añorve, Reynalda Roldan-Perez, Ali Flores-Perez, Omar Peña-Curiel, Oscar Angeles-Zaragoza, Rosalva Rangel Corona, Juan A Gonzalez-Barrios, Raul Bonilla-Moreno, Oscar Del Moral-Hernandez, Luis A Herrera, Alejandro Garcia-Carranca
Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells. Although the functional roles of microRNAs have been well described in lung cancer, their functional roles in radioresistance are largely unclear. In this study, we established a non-small cell lung carcinoma Calu-1 radioresistant cell line by continuous exposure to therapeutic doses of ionizing radiation as a model to investigate radioresistance-associated microRNAs...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345259/the-role-of-complement-inhibitors-beyond-controlling-inflammation
#11
REVIEW
A M Blom
The complement system is an arm of innate immunity that aids in the removal of pathogens and dying cells. Due to its harmful, pro-inflammatory potential, complement is controlled by several soluble and membrane-bound inhibitors. This family of complement regulators has been recently extended by the discovery of several new members, and it is becoming apparent that these proteins harbour additional functions. In this review, the current state of knowledge of the physiological functions of four complement regulators will be described: cartilage oligomeric matrix protein (COMP), CUB and sushi multiple domains 1 (CSMD1), sushi domain-containing protein 4 (SUSD4) and CD59...
March 26, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28344880/protective-function-of-interleukin-27-in-colitis-associated-cancer-via-suppression-of-inflammatory-cytokines-in-intestinal-epithelial-cells
#12
Bijun Cui, Shen Lu, Lihua Lai, Yiwei Xie, Jia He, Yue Xue, Peng Xiao, Ting Pan, Luoquan Chen, Yang Liu, Xuetao Cao, Qingqing Wang
Numerous studies have demonstrated that inflammation contributes to a variety of cancer formation, among them, colitis-associated cancer (CAC) represents a typical inflammation-related cancer. Interleukin 27 (IL-27) has been demonstrated to play an important role in inflammation-related disease. The effect of IL-27 in intestinal inflammation is controversial and its role in CAC is not elucidated yet. In our present study, we found that IL-27 has protective function in murine model of CAC through suppression of inflammatory cytokines in intestinal epithelial cells (IECs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344878/targeting-cytokine-signaling-checkpoint-cis-activates-nk-cells-to-protect-from-tumor-initiation-and-metastasis
#13
Eva M Putz, Camille Guillerey, Kevin Kos, Kimberley Stannard, Kim Miles, Rebecca B Delconte, Kazuyoshi Takeda, Sandra E Nicholson, Nicholas D Huntington, Mark J Smyth
The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344877/impact-of-chemo-radiotherapy-on-immune-cell-composition-and-function-in-cervical-cancer-patients
#14
H van Meir, R A Nout, M J P Welters, N M Loof, M L de Kam, J J van Ham, S Samuels, G G Kenter, A F Cohen, C J M Melief, J Burggraaf, M I E van Poelgeest, S H van der Burg
New treatments based on combinations of standard therapeutic modalities and immunotherapy are of potential use, but require a profound understanding of immune modulatory properties of standard therapies. Here, the impact of standard (chemo)radiotherapy on the immune system of cervical cancer patients was evaluated. Thirty patients with cervical cancer were treated with external beam radiation therapy (EBRT), using conventional three-dimensional or intensity modulated radiation therapy without constraints for bone marrow sparing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344866/cd13-hi-neutrophil-like-myeloid-derived-suppressor-cells-exert-immune-suppression-through-arginase-1-expression-in-pancreatic-ductal-adenocarcinoma
#15
Jing Zhang, Xiongfei Xu, Min Shi, Ying Chen, Danghui Yu, Chenyan Zhao, Yan Gu, Biao Yang, Shiwei Guo, Guiling Ding, Gang Jin, Chin-Lee Wu, Minghua Zhu
Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344639/aflatoxin-b1-inhibits-the-type-1-interferon-response-pathway-via-stat1-suggesting-another-mechanism-of-hepatocellular-carcinoma
#16
Patrick W Narkwa, David J Blackbourn, Mohamed Mutocheluh
BACKGROUND: Aflatoxin B1 (AFB1) contamination of food is very high in most sub-Saharan African countries. AFB1 is known to cause hepatocellular carcinoma (HCC) by inducing mutation in the tumour suppressor gene TP53. The number of new HCC cases is high in West Africa with an accompanying high mortality. The type I interferon (IFN) pathway of the innate immune system limits viral infections and exerts its anti-cancer property by up-regulating tumour suppressor activities and pro-apoptotic pathways...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28343174/mirna-analysis-in-pancreatic-cancer-the-dartmouth-experience
#17
Francine B de Abreu, Xiaoying Liu, Gregory J Tsongalis
Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%-90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm...
March 27, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28343076/repression-of-dok7-mediated-by-dnmt3a-promotes-the-proliferation-and-invasion-of-kyse410-and-te-12-escc-cells
#18
Shou-Mei Yang, Su-Yi Li, Hao-Bin Yu, Jie-Ru Li, Lei-Lei Sun
Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28342986/oncogenic-roles-of-dna-hypomethylation-through-the-activation-of-cancer-germline-genes
#19
Aurélie Van Tongelen, Axelle Loriot, Charles De Smet
Global loss of DNA methylation is frequently observed in the genome of human tumors. Although this epigenetic alteration is clearly associated with cancer progression, the way it exerts its pro-tumoral effect remains incompletely understood. A remarkable consequence of DNA hypomethylation in tumors is the aberrant activation of "cancer-germline" genes (also known as "cancer-testis" genes), which comprise a diverse group of germline-specific genes that use DNA methylation as a primary mechanism for repression in normal somatic tissues...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28341962/tumour-suppressor-ep300-a-modulator-of-paclitaxel-resistance-and-stemness-is-downregulated-in-metaplastic-breast-cancer
#20
Muhammad Asaduzzaman, Stephanie Constantinou, Haoxiang Min, John Gallon, Meng-Lay Lin, Poonam Singh, Selina Raguz, Simak Ali, Sami Shousha, R Charles Coombes, Eric W-F Lam, Yunhui Hu, Ernesto Yagüe
PURPOSE: We have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out...
March 24, 2017: Breast Cancer Research and Treatment
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