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https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#1
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28763841/-copy-number-aberrations-of-genes-related-to-extrohepatic-metastasis-free-survival-after-operation-for-hepatocellular-carcinoma
#2
L L Bao, Z Z Zhu, B J Wen, X X Wan, Y Q Ye, L Chen, S Q He, W M Cong
Objective: To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis. Results: Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2...
May 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28754852/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#3
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752701/-effects-of-myeloid-specific-deficiency-of-fbxw7-on-lung-metastasis-of-murine-melanoma
#4
Zhang Wei, Lai Lihua, Wang Qingqing
Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm(-)FBXW7(f/f) and Lysm(+)FBXW7 (f/f) mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed...
March 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28734796/clonal-composition-of-human-ovarian-cancer-based-on-copy-number-analysis-reveals-a-reciprocal-relation-with-oncogenic-mutation-status
#5
Kazuko Sakai, Masayo Ukita, Jeanette Schmidt, Longyang Wu, Marco A De Velasco, Alan Roter, Luis Jevons, Kazuto Nishio, Masaki Mandai
Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer. Genome-wide segmentation data consisting of the log2 ratio (log2R) and B allele frequency (BAF) were used to calculate an estimate of the clonal composition number (CC number) for each tumor...
July 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28727686/fbxw7-regulates-disc1-stability-via-the-ubiquitin-proteosome-system
#6
K Yalla, C Elliott, J P Day, J Findlay, S Barratt, Z A Hughes, L Wilson, E Whiteley, M Popiolek, Y Li, J Dunlop, R Killick, D R Adams, N J Brandon, M D Houslay, B Hao, G S Baillie
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#7
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer generally associated with an aggressive clinical behavior. Here we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs) and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28716020/long-non-coding-rna-casc2-suppresses-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells-through-casc2-mir-367-fbxw7-axis
#8
Yufeng Wang, Zhikui Liu, Bowen Yao, Qing Li, Liang Wang, Cong Wang, Changwei Dou, Meng Xu, Qingguang Liu, Kangsheng Tu
BACKGROUND: Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear. METHODS: The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC...
July 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28699179/colorectal-cancer-stem-cells-acquire-chemoresistance-through-the-upregulation-of-fbxw7-and-the-consequent-degradation-of-c-myc
#9
Daisuke Izumi, Takatsugu Ishimoto, Keisuke Miyake, Tsugio Eto, Kota Arima, Yuki Kiyozumi, Tomoyuki Uchihara, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Ajay Goel, Patrick Tan, Hideo Baba
The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. We previously established an LGR5(+) human colorectal cancer stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant non-cycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28685750/mir-497%C3%A2-195-cluster-regulates-angiogenesis-during-coupling-with-osteogenesis-by-maintaining-endothelial-notch-and-hif-1%C3%AE-activity
#10
Mi Yang, Chang-Jun Li, Xi Sun, Qi Guo, Ye Xiao, Tian Su, Man-Li Tu, Hui Peng, Qiong Lu, Qing Liu, Hong-Bo He, Tie-Jian Jiang, Min-Xiang Lei, Mei Wan, Xu Cao, Xiang-Hang Luo
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31(hi)Emcn(hi) vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31(hi)Emcn(hi) endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31(hi)Emcn(hi) vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31(hi)Emcn(hi) vessels and bone loss...
July 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#11
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28678173/molecular-and-clinicopathological-differences-by-age-at-the-diagnosis-of-colorectal-cancer
#12
Chu-Cheng Chang, Pei-Ching Lin, Chun-Chi Lin, Yuan-Tzu Lan, Hung-Hsin Lin, Chien-Hsing Lin, Shung-Haur Yang, Wen-Yi Liang, Wei-Shone Chen, Jeng-Kai Jiang, Jen-Kou Lin, Shih-Ching Chang
We compared the clinicopathological and molecular profiles between different age groups of sporadic colorectal cancer (CRC) patients (age <50, 56-60, 60-70, 70-80, and >80); 1475 CRC patients were enrolled after excluding 30 individuals with Lynch syndrome. The mutation spectra for APC, TP53, KRAS, PIK3CA, FBXW7, BRAF, NRAS, HRAS, TGFbR, Akt1, and PTEN were analyzed using polymerase chain reaction (PCR), followed by MassArray and microsatellite (MSI-high) analysis by performing genotyping. Male patients (74...
July 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28665315/myc-modulation-around-the-cdk2-p27-skp2-axis
#13
REVIEW
Per Hydbring, Alina Castell, Lars-Gunnar Larsson
MYC is a pleiotropic transcription factor that controls a number of fundamental cellular processes required for the proliferation and survival of normal and malignant cells, including the cell cycle. MYC interacts with several central cell cycle regulators that control the balance between cell cycle progression and temporary or permanent cell cycle arrest (cellular senescence). Among these are the cyclin E/A/cyclin-dependent kinase 2 (CDK2) complexes, the CDK inhibitor p27(KIP1) (p27) and the E3 ubiquitin ligase component S-phase kinase-associated protein 2 (SKP2), which control each other by forming a triangular network...
June 30, 2017: Genes
https://www.readbyqxmd.com/read/28662510/the-deubiquitinating-enzyme-usp14-regulates-leukemic-chemotherapy-drugs-induced-cell-apoptosis-by-suppressing-ubiquitination-of-aurora-kinase-b
#14
Chunge Song, Ruojin Ma, Xiaoyu Yang, Sulei Pang
BACKGROUND/AIMS: Aurora kinase B is a mitotic checkpoint kinase that plays a pivotal role in mitosis by ensuring correct chromosome segregation and normal progression through mitosis. Aurora B has been found to be amplified and overexpressed in several types of leukemia. The deubiquitinating enzyme USP14 is one of three proteasome-associated deubiquitinating enzymes and plays critical roles in diverse biological processes including cancer. However, whether USP14 has a role in leukemia cells remains elusive...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28656290/mir-367-promotes-tumor-growth-by-inhibiting-fbxw7-in-nsclc
#15
Guodong Xiao, Xiao Gao, Xin Sun, Chengcheng Yang, Boxiang Zhang, Ruiying Sun, Guanghong Huang, Xiang Li, Jian Liu, Ning Du, Dapeng Liu, Rui Liang, Hong Ren, Sida Qin
miR-367 is one of the most abundant miRNAs in human embryonic stem cells (hESCs) and is mainly involved in maintaining the pluripotency of stem cells. However, its role in cancer development remains poorly understood. In the present study, we explored the function and mechanism of the endogenous miR-367 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the level of miR-367 in NSCLC was significantly higher than that in adjacent normal tissues, and its upregulation was positively correlated with tumor size, tumor differentiation and tumor-node-metastasis (TNM) stage...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28644144/meta-analysis-of-the-clinical-characteristics-and-prognostic-relevance-of-notch1-and-fbxw7-mutation-in-t-cell-acute-lymphoblastic-leukemia
#16
Rong-Bin Liu, Jian-Gui Guo, Tian-Ze Liu, Cheng-Cheng Guo, Xin-Xiang Fan, Xiao Zhang, Xiu-Yu Cai, Wei-Han Hu
The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619094/morphologic-and-molecular-study-of-lung-cancers-associated-with-idiopathic-pulmonary-fibrosis-and-other-pulmonary-fibroses
#17
Alice Guyard, Claire Danel, Nathalie Théou-Anton, Marie-Pierre Debray, Laure Gibault, Pierre Mordant, Yves Castier, Bruno Crestani, Gérard Zalcman, Hélène Blons, Aurélie Cazes
BACKGROUND: Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). METHODS: Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28581676/comprehensive-genomic-profiling-of-different-subtypes-of-nasopharyngeal-carcinoma-reveals-similarities-and-differences-to-guide-targeted-therapy
#18
Siraj M Ali, Ming Yao, Jicheng Yao, Jing Wang, Yuwei Cheng, Alexa B Schrock, Gung-Wei Chirn, Hui Chen, Shuo Mu, Laurie Gay, Julia A Elvin, James Suh, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Kai Wang
BACKGROUND: To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs). METHODS: Comprehensive genomic profiling was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC)...
June 5, 2017: Cancer
https://www.readbyqxmd.com/read/28581525/ck1%C3%AE-gsk3%C3%AE-fbxw7%C3%AE-axis-promotes-degradation-of-the-znf322a-oncoprotein-to-suppress-lung-cancer-progression
#19
S-Y Liao, C-W Chiang, C-H Hsu, Y-T Chen, J Jen, H-F Juan, W-W Lai, Y-C Wang
Overexpression of Cys2His2 zinc-finger 322A (ZNF322A) oncogenic transcription factor is associated with lung tumorigenesis. However, the mechanism of ZNF322A overexpression remains poorly understood. Here, we discover that protein stability of ZNF322A is regulated by coordinated phosphorylation and ubiquitination through the CK1δ/GSK3β/FBXW7α axis. CK1δ and GSK3β kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7α leading to ZNF322A protein destruction...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28575849/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#20
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
May 17, 2017: Oncotarget
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