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https://www.readbyqxmd.com/read/29748662/reducing-protein-regulator-of-cytokinesis-1-as-a-prospective-therapy-for-hepatocellular-carcinoma
#1
Xinran Liu, Yangkai Li, Lijing Meng, Xin-Yuan Liu, Anlin Peng, Yuchen Chen, Chengyu Liu, Hong Chen, Sheng Sun, Xiaoping Miao, Yu Zhang, Ling Zheng, Kun Huang
Proteins that bind to microtubule are important for cell cycle, and some of these proteins show oncogenic characteristics with mechanisms not fully understood. Herein we demonstrate overexpression of protein regulator of cytokinesis 1 (PRC1), a microtubule-associated regulator of mitosis, in human hepatocellular carcinoma (HCC). Moreover, upregulated PRC1 is associated with lower survival rates of HCC patients. Mechanistically, reducing PRC1 blocks mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29728595/pkc-dependent-p14arf-phosphorylation-on-threonine-8-drives-cell-proliferation
#2
Rosa Fontana, Daniela Guidone, Felicia Sangermano, Viola Calabrò, Alessandra Pollice, Girolama La Mantia, Maria Vivo
ARF role as tumor suppressor has been challenged in the last years by several findings of different groups ultimately showing that its functions can be strictly context dependent. We previously showed that ARF loss in HeLa cells induces spreading defects, evident as rounded morphology of depleted cells, accompanied by a decrease of phosphorylated Focal Adhesion Kinase (FAK) protein levels and anoikis. These data, together with previous finding that a PKC dependent signalling pathway can lead to ARF stabilization, led us to the hypothesis that ARF functions in cell proliferation might be regulated by phosphorylation...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29676649/asbestos-induces-epigenetic-repression-of-ras-association-domain-containing-protein-1-p16-kinase-4a-inhibitor-and-p14-alternative-reading-frame-in-normal-human-mesothelial-cells
#3
Sichuan Xi, Eden C Payabyab, David M Straughan, Emily S Reardon, Mary Zhang, Julie A Hong, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2 ) for up to 10 days...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29676355/the-determination-of-stage-in-nonmuscle-urothelial-carcinoma-staining-pattern-of-caspase-8
#4
Nilay Şen Türk, Saadettin Eskiçorapçi, Zafer Aybek, Levent Tuncay
Context: Urothelial carcinoma (UC) is one of the most frequent epithelial tumors worldwide. Aims: We aimed to investigate the protein expressions of caspase-8, p53, murine double minute 2 (mdm2), and p14ARF in nonmuscle UCs and to correlate the findings with clinicopathological characteristics. Settings and Design: A total of 50 patients who had pTa and pT1 tumors were analyzed. Subjects and Methods: The protein expressions of caspase-8, p53, mdm2, and p14ARF were analyzed by immunohistochemistry...
April 2018: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29629612/the-9p21-locus-as-a-potential-therapeutic-target-and-prognostic-marker-in-colorectal-cancer
#5
Afsane Bahrami, Seyed Mahdi Hassanian, Majid Khazaei, Masoumeh Gharib, Mahsa Rahmani, Hamid Fiuji, Mir Hadi Jazayeri, Mehrdad Moetamani-Ahmadi, Gordon A Ferns, Amir Avan
Colorectal cancer (CRC) is a major cause of cancer-related-death worldwide. Despite extensive efforts to identify valid biomarkers for the risk stratification of CRC patients, there are few of proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to CRC. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CRC. Several genetic polymorphisms have been identified in this region that are associated with CRC...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29472714/oncogene-induced-senescence-mediated-by-c-myc-requires-usp10-dependent-deubiquitination-and-stabilization-of-p14arf
#6
Aram Ko, Su Yeon Han, Chel Hun Choi, Hanbyoul Cho, Min-Sik Lee, Soo-Youl Kim, Joon Seon Song, Kyeong-Man Hong, Han-Woong Lee, Stephen M Hewitt, Joon-Yong Chung, Jaewhan Song
Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10)...
February 22, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29435041/tbx2-expression-is-associated-with-platinum-sensitivity-of-ovarian-serous-carcinoma
#7
Reiko Tasaka, Takeshi Fukuda, Masahiro Shimomura, Yuta Inoue, Takuma Wada, Masaru Kawanishi, Tomoyo Yasui, Toshiyuki Sumi
The standard treatment for ovarian serous carcinoma comprises maximum debulking surgery and platinum-based chemotherapy. Despite the high response rate to chemotherapy, the majority of patients will be resistant to first-line agents and the prognosis for these patients is particularly poor. At present there are no reliable methods to determine or predict platinum resistance. T-box 2 (TBX2) is widely expressed in cancer cells and is involved in embryonic development and cell cycle regulation. TBX2 enables cells to bypass senescence through its ability to repress the cell cycle regulators p21 and p14ARF ; silencing TBX2 induces senescence...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29435006/prl-3-promotes-breast-cancer-progression-by-downregulating-p14-arf-mediated-p53-expression
#8
Hua Xie, Hao Wang
Prior studies have demonstrated that phosphatase of regenerating liver-3 (PRL-3) serves avital function in cell proliferation and metastasis in breast cancer. However, the molecular mechanisms underlying the function of PRL-3 in breast cancer remain unknown. PRL-3 expression was analyzed in 24 pairs of breast cancer and normal tissues using the reverse transcription-quantitative polymerase chain reaction assay. The results of the present study identified that the expression of PLR-3 in breast cancer tissues was increased 4...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29360938/long-term-persistent-organic-pollutants-exposure-induced-telomere-dysfunction-and-senescence-associated-secretary-phenotype
#9
Jinghua Yuan, Yang Liu, Juan Wang, Yuxia Zhao, Keqiu Li, Yaqing Jing, Xiaoning Zhang, Qiang Liu, Xin Geng, Guang Li, Feng Wang
Environmentally persistent organic pollutant (POPs) is the general term for refractory organic compounds that show long-range atmospheric transport, environmental persistence, and bioaccumulation. It has been reported that the accumulation of POPs could lead to cellular DNA damage and adverse effects of on metabolic health. To better understand the mechanism of the health risks associated with POPs, we conducted an evidence based cohort investigation (n=5955) at the Jinghai e-waste disposal center in China from 2009-2016, where people endure serious POPs exposure...
January 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29340077/lrp6-targeting-suppresses-gastric-tumorigenesis-via-p14-arf-mdm2-p53-dependent-cellular-senescence
#10
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo ...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29283500/identification-of-a-novel-nucleophosmin-interaction-motif-in-the-tumor-suppressor-p14arf
#11
EDITORIAL
Enrico Luchinat, Sara Chiarella, Mimma Franceschini, Adele Di Matteo, Maurizio Brunori, Lucia Banci, Luca Federici
The tumor suppressor p14arf interacts, in response to oncogenic signals, with the p53 E3-ubiquitin ligase HDM2, thereby resulting in p53 stabilization and activation. In addition, it also exerts tumor-suppressive functions in p53-independent contexts. The activities of p14arf are regulated by the nucleolar chaperone nucleophosmin (NPM1), which controls its levels and cellular localization. In acute myeloid leukemia with mutations in the NPM1 gene, mutated NPM1 aberrantly translocates in the cytosol carrying with itself p14arf that is subsequently degraded, thus impairing the p14arf-HDM2-p53 axis...
March 2018: FEBS Journal
https://www.readbyqxmd.com/read/29240242/the-9p21-locus-a-potential-therapeutic-target-and-prognostic-marker-in-breast-cancer
#12
REVIEW
Mahdi Rivandi, Mohammad-Sadegh Khorrami, Hamid Fiuji, Soodabeh Shahidsales, Malihe Hasanzadeh, Mir Hadi Jazayeri, Seyed Mahdi Hassanian, Gordon A Ferns, Nafiseh Saghafi, Amir Avan
Breast cancer is an important cause of cancer related mortality in women. Despite extensive efforts to identify valid biomarkers for risk stratification, there are relatively few with proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to breast cancer. Recent genome-wide-association-studies and gene expression analysis have demonstrated that a locus on chromosome 9p21, which contains three genes; CDKN2B (encoding p15ink4b), CDKN2A (encoding p16ink4a and p14ARF) and the 3' end of CDKN2BAS (an antisense noncoding RNA in the INK4 locus [ANRIL]) are associated with an increased risk of this malignancy...
December 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29228217/p19arf-inhibits-aggressive-progression-of-h-ras-driven-hepatocellular-carcinoma
#13
Dragana Kopanja, Shuo Huang, Mohamed Rizwan Haroon Al Raheed, Grace Guzman, Pradip Raychaudhuri
Arf, a well-established tumor suppressor, is either mutated or downregulated in a wide array of cancers. However, its role in hepatocellular carcinoma (HCC) progression is controversial. Conflicting observations have been published regarding its expression in HCC. In this study, we provide clear genetic evidence demonstrating a protective role of p19Arf in hepatocarcinogenesis. Using Ras-induced mouse model, we show that p19Arf deficiency accelerates progression of aggressive HCC in vivo. To investigate the role of p14ARF in human liver cancers, we analyzed its expression in human HCC using immunohistochemistry (IHC)...
March 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29115399/loss-of-the-clock-gene-per2-is-associated-with-cancer-development-and-altered-expression-of-important-tumor-related-genes-in-oral-cancer
#14
Honggang Xiong, Yixin Yang, Kai Yang, Dan Zhao, Hong Tang, Xiongwen Ran
Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types. However, the expression of PER2 in oral squamous cell carcinoma (OSCC), a common malignant tumor in humans, and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear. In the present study, we detected the mRNA and protein expression levels of PER2, PIK3CA, PTEN, P53, P14ARF and caspase‑8 in OSCC tissues and cancer-adjacent oral mucosa by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry...
October 31, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28754531/carf-is-a-multi-module-regulator-of-cell-proliferation-and-a-molecular-bridge-between-cellular-senescence-and-carcinogenesis
#15
REVIEW
Renu Wadhwa, Rajkumar Singh Kalra, Sunil C Kaul
CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or -independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. CARF-driven control over p53-HDM2-p21(WAF1) axis was shown to regulate cell proliferative fates. Cells with CARF-overexpression (CARF-OE) and superexpression (CARF-SE) showed growth arrest and pro-proliferative phenotypes, respectively...
July 25, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28711940/clinical-significance-of-p16ink4a-and-p14arf-promoter-methylation-in-renal-cell-carcinoma-a-meta-analysis
#16
Yu Ren, Li Xiao, Guobin Weng, Bingyi Shi
The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#17
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28436949/p14arf-interacts-with-the-focal-adhesion-kinase-and-protects-cells-from-anoikis
#18
M Vivo, R Fontana, M Ranieri, G Capasso, T Angrisano, A Pollice, V Calabrò, G La Mantia
The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase...
August 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28431405/usp5-functions-as-an-oncogene-for-stimulating-tumorigenesis-in-hepatocellular-carcinoma
#19
Yi Liu, Wei-Mao Wang, Ying-Fei Lu, Lu Feng, Li Li, Ming-Zhu Pan, Yu Sun, Chun-Wai Suen, Wei Guo, Jian-Xin Pang, Jin-Fang Zhang, Wei-Ming Fu
As deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis. It was found that Usp5 was significantly upregulated in hepatocellular carcinoma (HCC) cells and most clinical specimens. Further functional investigation also showed that Usp5 knockdown suppressed cell proliferation, migration, drug resistance and induced apoptosis; on the other hand, Usp5 overexpression promoted colony formation, migration, drug resistance and tumorigenesis...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28265066/resistance-mechanisms-to-tp53-mdm2-inhibition-identified-by-in-vivo-piggybac-transposon-mutagenesis-screen-in-an-arf-mouse-model
#20
Emilie A Chapeau, Agnieszka Gembarska, Eric Y Durand, Emeline Mandon, Claire Estadieu, Vincent Romanet, Marion Wiesmann, Ralph Tiedt, Joseph Lehar, Antoine de Weck, Roland Rad, Louise Barys, Sebastien Jeay, Stephane Ferretti, Audrey Kauffmann, Esther Sutter, Armelle Grevot, Pierre Moulin, Masato Murakami, William R Sellers, Francesco Hofmann, Michael Rugaard Jensen
Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
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