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https://www.readbyqxmd.com/read/27919789/unravelling-a-p73-regulated-network-the-role-of-a-novel-p73-dependent-target-mir3158-in-cancer-cell-migration-and-invasiveness
#1
Sotiris Galtsidis, Stella Logotheti, Athanasia Pavlopoulou, Christos P Zampetidis, Georgia Papachristopoulou, Andreas Scorilas, Borek Vojtesek, Vassilis Gorgoulis, Vassilis Zoumpourlis
The transcription factor p73 is homologous to the well-known tumor-suppressor p53. The p73-regulated networks are of significant clinical interest, because they may substitute for impaired p53-regulated networks which are commonly perturbed in cancer. Herein, we aimed to characterize a p73-regulated network that mediates cell migration and restores anti-oncogenic responses in p53-mutant cancer cells. In this study, we demonstrate that p73 regulates a network underlying cell migration, which consists of MIR34A/MIR3158/vimentin/β-catenin/lef1...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#2
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889317/the-p53-family-coordinates-wnt-and-nodal-inputs-in-mesendodermal-differentiation-of-embryonic-stem-cells
#3
Qiong Wang, Yilong Zou, Sonja Nowotschin, Sang Yong Kim, Qing V Li, Chew-Li Soh, Jie Su, Chao Zhang, Weiping Shu, Qiaoran Xi, Danwei Huangfu, Anna-Katerina Hadjantonakis, Joan Massagué
In this study, we outline a regulatory network that involves the p53 tumor suppressor family and the Wnt pathway acting together with the TGF-β pathway in mesendodermal differentiation of mouse and human embryonic stem cells. Knockout of all three members, p53, p63, and p73, shows that the p53 family is essential for mesendoderm specification during exit from pluripotency in embryos and in culture. Wnt3 and its receptor Fzd1 are direct p53 family target genes in this context, and induction of Wnt signaling by p53 is critical for activation of mesendodermal differentiation genes...
November 9, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27884017/the-p53-family-orchestrates-the-regulation-of-metabolism-physiological-regulation-and-implications-for-cancer-therapy
#4
Marco Napoli, Elsa R Flores
The p53 family of transcription factors is essential to counteract tumour formation and progression. Although previously this was exclusively associated with the ability of the p53 family to induce cell cycle arrest and apoptosis, an increasing number of reports have now indisputably demonstrated that the tumour suppressive functions of the p53 family members also rely on their ability to control and regulate cellular metabolism and maintain cellular oxidative homeostasis. Here, we review how each p53 family member, including p63 and p73, controls metabolic pathways in physiological conditions, and how these mechanisms could be exploited to provide anticancer therapeutic opportunities...
November 24, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27878984/sulforaphane-induced-apoptosis-in-xuanwei-lung-adenocarcinoma-cell-line-xwlc-05
#5
Lan Zhou, Qian Yao, Yan Li, Yun-Chao Huang, Hua Jiang, Chuan-Qiong Wang, Lei Fan
BACKGROUND: Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non-smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL-05) to explore the value of sulforaphane in lung cancer prevention and treatment...
November 23, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27866875/p53-and-p73-regulate-apoptosis-but-not-cell-cycle-progression-in-mouse-embryonic-stem-cells-upon-dna-damage-and-differentiation
#6
Hanbing He, Cheng Wang, Qian Dai, Fengtian Li, Johann Bergholz, Zhonghan Li, Qintong Li, Zhi-Xiong Xiao
Embryonic stem cells (ESCs) are fast proliferating cells capable of differentiating into all somatic cell types. In somatic cells, it is well documented that p53 is rapidly activated upon DNA damage to arrest the cell cycle and induce apoptosis. In mouse ESCs, p53 can also be functionally activated, but the precise biological consequences are not well characterized. Here, we demonstrated that doxorubicin treatment initially led to cell-cycle arrest at G2/M in ESCs, followed by the occurrence of massive apoptosis...
November 16, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27865929/g2-m-cell-cycle-arrest-on-ht-29-cancer-cells-and-toxicity-assessment-of-triphenylphosphanegold-i-carbonimidothioates-ph3pau-sc-or-nph-r-me-et-and-ipr-during-zebrafish-development
#7
Kah Kooi Ooi, Chien Ing Yeo, Theventhiran Mahandaran, Kok Pian Ang, Abdah Md Akim, Yoke-Kqueen Cheah, Hoi-Ling Seng, Edward R T Tiekink
Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death...
November 4, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27835605/meta-analysis-of-dna-methylation-biomarkers-in-hepatocellular-carcinoma
#8
Cheng Zhang, Jinyun Li, Tao Huang, Shiwei Duan, Dongjun Dai, Danjie Jiang, Xinbing Sui, Da Li, Yidan Chen, Fei Ding, Changxin Huang, Gongying Chen, Kaifeng Wang
DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832139/a-subpopulation-of-the-k562-cells-are-killed-by-curcumin-treatment-after-g2-m-arrest-and-mitotic-catastrophe
#9
Macario Martinez-Castillo, Raul Bonilla-Moreno, Leticia Aleman-Lazarini, Marco Antonio Meraz-Rios, Lorena Orozco, Leticia Cedillo-Barron, Emilio J Cordova, Nicolas Villegas-Sepulveda
Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe...
2016: PloS One
https://www.readbyqxmd.com/read/27825141/p73-expression-is-regulated-by-ribosomal-protein-rpl26-through-mrna-translation-and-protein-stability
#10
Min Zhang, Jin Zhang, Wensheng Yan, Xinbin Chen
p73, a p53 family tumor suppressor, is regulated by multiple mechanisms, including transcription and mRNA and protein stability. However, whether p73 expression is regulated via mRNA translation has not been explored. To test this, we examined whether ribosomal protein 26 (RPL26) plays a role in p73 expression. Here, we showed that p73 expression is controlled by RPL26 via protein stability and mRNA translation. To examine whether MDM2 mediates RPL26 to regulate p73 protein stability, we generated multiple MDM2-knockout cell lines by CRISPR-cas9...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27807512/lipopolysaccharide-induces-human-pulmonary-micro-vascular-endothelial-apoptosis-via-the-yap-signaling-pathway
#11
Lei Yi, Xiaoqin Huang, Feng Guo, Zengding Zhou, Mengling Chang, Jiajun Tang, Jingning Huan
Gram-negative bacterial lipopolysaccharide (LPS) induces a pathologic increase in lung vascular leakage under septic conditions. LPS-induced human pulmonary micro-vascular endothelial cell (HPMEC) apoptosis launches and aggravates micro-vascular hyper-permeability and acute lung injury (ALI). Previous studies show that the activation of intrinsic apoptotic pathway is vital for LPS-induced EC apoptosis. Yes-associated protein (YAP) has been reported to positively regulate intrinsic apoptotic pathway in tumor cells apoptosis...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27721608/argyrophilic-nuclear-organizer-region-and-p73-expression-in-head-and-neck-squamous-cell-carcinomas-teammates-or-adversaries
#12
Sunil Pazhayanur Venkateswaran, Leviana Ercylina Nathan, Vimi Sunil Mutalik, Noor Hasni Shamsuddin
CONTEXT: Head and neck squamous cell carcinoma (HNSCC) consists of squamous cell carcinomas (SCCs) arising in the upper aerodigestive tract and accounts for 5% of cancers worldwide. In Malaysia, cancers of the nasopharynx, larynx, tongue and oral cavity are among the top twenty most common cancers in men. Argyrophilic nuclear organizer regions (AgNORs) are increased from normal mucosa to premalignant lesions to malignant lesions and have been associated with tumor grade and prognosis of patients...
September 2016: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/27716744/mechanism-of-tap73-inhibition-by-%C3%AE-np63-and-structural-basis-of-p63-p73-hetero-tetramerization
#13
Jakob Gebel, Laura M Luh, Daniel Coutandin, Christian Osterburg, Frank Löhr, Birgit Schäfer, Ann-Sophie Frombach, Manuela Sumyk, Lena Buchner, Tobias Krojer, Eidarus Salah, Sebastian Mathea, Peter Güntert, Stefan Knapp, Volker Dötsch
Members of the p53 tumor-suppressor family are expressed as multiple isoforms. Isoforms with an N-terminal transactivation domain are transcriptionally active, while those ones lacking this domain often inhibit the transcriptional activity of other family members. In squamous cell carcinomas, the high expression level of ΔNp63α inhibits the tumor-suppressor function of TAp73β. This can in principle be due to blocking of the promoter or by direct interaction between both proteins. p63 and p73 can hetero-oligomerize through their tetramerization domains and a hetero-tetramer consisting of two p63 and two p73 molecules is thermodynamically more stable than both homo-tetramers...
December 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27622714/crocetin-exploits-p53-induced-death-domain-pidd-and-fas-associated-death-domain-fadd-proteins-to-induce-apoptosis-in-colorectal-cancer
#14
Pallab Ray, Deblina Guha, Juni Chakraborty, Shuvomoy Banerjee, Arghya Adhikary, Samik Chakraborty, Tanya Das, Gaurisankar Sa
Tumor suppressor p53 preserves the genomic integrity by restricting anomaly at the gene level. The hotspots for mutation in half of all colon cancers reside in p53. Hence, in a p53-mutated cellular milieu targeting cancer cells may be achievable by targeting the paralogue(s) of p53. Here we have shown the effectiveness of crocetin, a dietary component, in inducing apoptosis of colon cancer cells with varying p53 status. In wild-type p53-expressing cancer cells, p53 in one hand transactivates BAX and in parallel up-regulates p53-induced death domain protein (PIDD) that in turn cleaves and activates BID through caspase-2...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27619483/targeting-tead-yap-transcription-dependent-necrosis-triad-ameliorates-huntington-s-disease-pathology
#15
Ying Mao, Xigui Chen, Min Xu, Kyota Fujita, Kazumi Motoki, Toshikazu Sasabe, Hidenori Homma, Miho Murata, Kazuhiko Tagawa, Takuya Tamura, Julia Kaye, Steven Finkbeiner, Giovanni Blandino, Marius Sudol, Hitoshi Okazawa
Neuronal cell death in neurodegenerative diseases is not fully understood. Here we report that mutant huntingtin (Htt), a causative gene product of Huntington's diseases (HD) selectively induces a new form of necrotic cell death, in which endoplasmic reticulum (ER) enlarges and cell body asymmetrically balloons and finally ruptures. Pharmacological and genetic analyses revealed that the necrotic cell death is distinct from the RIP1/3 pathway-dependent necroptosis, but mediated by functional deficiency of TEAD/YAP-dependent transcription...
September 12, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27600721/aggregation-tendencies-in-the-p53-family-are-modulated-by-backbone-hydrogen-bonds
#16
Elio A Cino, Iaci N Soares, Murilo M Pedrote, Guilherme A P de Oliveira, Jerson L Silva
The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27599791/sh003-selectively-induces-p73%C3%A2-dependent-apoptosis-in-triple%C3%A2-negative-breast-cancer-cells
#17
Eun Kyoung Choi, Seung-Mi Kim, Seung-Woo Hong, Jai-Hee Moon, Jae-Sik Shin, Jeong Hee Kim, Ih-Yeon Hwang, Soo-A Jung, Dae-Hee Lee, Eun Young Lee, Seul Lee, Hyunwoo Kim, Daejin Kim, Yeong Seok Kim, Youn Kyung Choi, Hyo In Kim, Hyeong Sim Choi, Sung-Gook Cho, Jeong Eun Kim, Kyu Pyo Kim, Yong Sang Hong, Won Keun Lee, Jung Shin Lee, Tae Won Kim, Seong-Gyu Ko, Dong-Hoon Jin
Triple-negative breast cancer (TNBC) is a breast cancer subtype that has an aggressive phenotype, is highly metastatic, has limited treatment options and is associated with a poor prognosis. In addition, metastatic TNBC has no preferred standard chemotherapy due to resistance to anthracyclines and taxanes. The present study demonstrated that a herbal extract, SH003, reduced cell viability and induced apoptosis in TNBC without cell cytotoxicity. Cell viability was examined using trypan blue exclusion and colony formation assays, which revealed a decrease in the cell viability...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27589690/the-dominant-negative-interplay-between-p53-p63-and-p73-a-family-affair
#18
Olivier Billant, Alice Léon, Solenn Le Guellec, Gaëlle Friocourt, Marc Blondel, Cécile Voisset
The tumor suppression activity of p53 is frequently impaired in cancers even when a wild-type copy of the gene is still present, suggesting that a dominant-negative effect is exerted by some of p53 mutants and isoforms. p63 and p73, which are related to p53, have also been reported to be subjected to a similar loss of function, suggesting that a dominant-negative interplay might happen between p53, p63 and p73. However, to which extent p53 hotspot mutants and isoforms of p53, p63 and p73 are able to interfere with the tumor suppressive activity of their siblings as well as the underlying mechanisms remain undeciphered...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27588182/dna-methylation-and-leukemia-susceptibility-in-china-evidence-from-an-updated-meta-analysis
#19
Danjie Jiang, Yirun Li, Qingxiao Hong, Yusheng Shen, Chunjing Xu, Yan Xu, Huangkai Zhu, Dongjun Dai, Guifang Ouyang, Shiwei Duan
Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated...
September 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27549118/aggregation-and-prion-like-properties-of-misfolded-tumor-suppressors-is-cancer-a-prion-disease
#20
Danielly C F Costa, Guilherme A P de Oliveira, Elio A Cino, Iaci N Soares, Luciana P Rangel, Jerson L Silva
Prion diseases are disorders that share several characteristics that are typical of many neurodegenerative diseases. Recently, several studies have extended the prion concept to pathological aggregation in malignant tumors involving misfolded p53, a tumor-suppressor protein. The aggregation of p53 and its coaggregation with p53 family members, p63 and p73, have been shown. Certain p53 mutants exert a dominant-negative regulatory effect on wild-type (WT) p53. The basis for this dominant-negative effect is that amyloid-like mutant p53 converts WT p53 into an aggregated species, leading to a gain-of-function (GoF) phenotype and the loss of its tumor-suppressor function...
October 3, 2016: Cold Spring Harbor Perspectives in Biology
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