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FBXW7

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https://www.readbyqxmd.com/read/28424412/fbxw7-missense-mutation-a-novel-negative-prognostic-factor-in-metastatic-colorectal-adenocarcinoma
#1
Krittiya Korphaisarn, Van Karlyle Morris, Michael J Overman, David R Fogelman, Bryan K Kee, Kanwal Pratap Singh Raghav, Shanequa Manuel, Imad Shureiqi, Robert A Wolff, Cathy Eng, David Menter, Stanley R Hamilton, Scott Kopetz, Arvind Dasari
BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associated with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not been described. METHODS: Data were obtained from mCRC patients whose tumors were evaluated by next-generation sequencing for hotspot mutations at The University of Texas MD Anderson Cancer Center...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423622/hnrnpk-mir-223-fbxw7-feedback-cascade-promotes-pancreatic-cancer-cell-growth-and-invasion
#2
D He, Cheng Huang, Qingxin Zhou, Dawei Liu, Longhui Xiong, Hongxia Xiang, Guangnian Ma, Zhiyong Zhang
Several studies have identified miR-223 critically involved in various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action and regulatory mechanisms in PDAC remains largely unclear. In this study, we found that the expression levels of miR-223 were increased in clinical samples with PDAC (81.6%). The upregulation of miR-223 increases the proliferation, migration, and invasive abilities of PDAC cells in vitro and in vivo. Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7 reverted miR-223- induced drastic proliferation in PDAC cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422719/fbxw7-haploinsufficiency-loses-its-protection-against-dna-damage-and-accelerates-mnu-induced-gastric-carcinogenesis
#3
Yannan Jiang, Xinming Qi, Xinyu Liu, Jun Zhang, Jun Ji, Zhenggang Zhu, Jin Ren, Yingyan Yu
Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor suppressor via inducing apoptosis and growth arrest in various kinds of tumors. To clarify the initiating role in gastric carcinogenesis as well as the histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408485/styx-a-versatile-pseudophosphatase
#4
REVIEW
Veronika Reiterer, Krzysztof Pawłowski, Hesso Farhan
The pseudophosphatase STYX (serine/threonine/tyrosine interacting protein) is a catalytically inactive member of the protein tyrosine phosphatase family. We perform a phylogenetic analysis of STYX and ask how far does the pseudoenzyme status of STYX reaches in evolution. Based on our previous work, we use STYX as a showcase to discuss four basic modes of action that any given pseudoenzyme may exert. Our previous work on the effect of STYX on mitogen-activated protein kinase (MAPK) signaling led us to identify two complementary modes of action...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28407575/fam83d-knockdown-regulates-proliferation-migration-and-invasion-of-colorectal-cancer-through-inhibiting-fbxw7-notch-1-signalling-pathway
#5
Yu Mu, Hongzhi Zou, Beibei Chen, Yixiao Fan, Suxia Luo
Colorectal cancer is one of the most common malignant tumors in the digestive system, and in China its incidence is rising in recent years. The FAM83D family with sequence similarity 83, member D is associated with the occurrence and development of various cancers. However, in human colorectal cancer, the biological function of FAM83D and its molecular mechanism are still little known. In our study, we found that FAM83D mRNA expression level was markedly up-regulated in colorectal cancerous tissues when compared with that of adjacent normal colon tissues...
April 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#6
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399885/next-generation-sequencing-and-fish-studies-reveal-the-appearance-of-gene-mutations-and-chromosomal-abnormalities-in-hematopoietic-progenitors-in-chronic-lymphocytic-leukemia
#7
Miguel Quijada-Álamo, María Hernández-Sánchez, Cristina Robledo, Jesús-María Hernández-Sánchez, Rocío Benito, Adrián Montaño, Ana E Rodríguez-Vicente, Dalia Quwaider, Ana-África Martín, María García-Álvarez, María Jesús Vidal-Manceñido, Gonzalo Ferrer-Garrido, María-Pilar Delgado-Beltrán, Josefina Galende, Juan-Nicolás Rodríguez, Guillermo Martín-Núñez, José-María Alonso, Alfonso García de Coca, José A Queizán, Magdalena Sierra, Carlos Aguilar, Alexander Kohlmann, José-Ángel Hernández, Marcos González, Jesús-María Hernández-Rivas
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as a mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, the presence of both chromosomal aberrations and gene mutations in CD34+ cells from the same patients has not been explored. METHODS: Amplicon-based deep next-generation sequencing (NGS) studies were carried out in magnetically activated-cell-sorting separated CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1 genes...
April 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28292439/integrated-molecular-characterization-of-uterine-carcinosarcoma
#8
Andrew D Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A Soslow, Russell R Broaddus, Rosemary E Zuna, Gordon Robertson, Peter W Laird, Raju Kucherlapati, Gordon B Mills, John N Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A Levine
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28287082/e3-ligase-fbxw7-is-critical-for-rig-i-stabilization-during-antiviral-responses
#9
Yinjing Song, Lihua Lai, Zhenlu Chong, Jia He, Yuanyuan Zhang, Yue Xue, Yiwei Xie, Songchang Chen, Ping Dong, Luoquan Chen, Zhimin Chen, Feng Dai, Xiaopeng Wan, Peng Xiao, Xuetao Cao, Yang Liu, Qingqing Wang
Viruses can escape from host recognition by degradation of RIG-I or interference with the RIG-I signalling to establish persistent infections. However, the mechanisms by which host cells stabilize RIG-I protein for avoiding its degradation are largely unknown. We report here that, upon virus infection, the E3 ubiquitin ligase FBXW7 translocates from the nucleus into the cytoplasm and stabilizes RIG-I. FBXW7 interacts with SHP2 and mediates the degradation and ubiquitination of SHP2, thus disrupting the SHP2/c-Cbl complex, which mediates RIG-I degradation...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#10
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#11
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28256213/update-on-molecular-findings-in-rhabdomyosarcoma
#12
REVIEW
Dina El Demellawy, Jean McGowan-Jordan, Joseph de Nanassy, Elizaveta Chernetsova, Ahmed Nasr
Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS...
April 2017: Pathology
https://www.readbyqxmd.com/read/28243320/construction-of-a-multiplex-mutation-hot-spot-pcr-panel-the-first-step-towards-colorectal-cancer-genotyping-on-the-gs-junior-platform
#13
Bálint Péterfia, Alexandra Kalmár, Árpád V Patai, István Csabai, András Bodor, Tamás Micsik, Barnabás Wichmann, Krisztina Egedi, Péter Hollósi, Ilona Kovalszky, Zsolt Tulassay, Béla Molnár
Background: To support cancer therapy, development of low cost library preparation techniques for targeted next generation sequencing (NGS) is needed. In this study we designed and tested a PCR-based library preparation panel with limited target area for sequencing the top 12 somatic mutation hot spots in colorectal cancer on the GS Junior instrument. Materials and Methods: A multiplex PCR panel was designed to amplify regions of mutation hot spots in 12 selected genes (APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#14
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#15
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196911/pseudophosphatase-as-e3-ubiquitin-ligase-inhibitor
#16
Nancy R Gough
The pseudophosphatase STYX prevents the substrate recognition subunit FBXW7 from binding the catalytic E3 ubiquitin ligase complex.
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28194040/abnormal-degradation-of-the-neuronal-stress-protective-transcription-factor-hsf1-in-huntington-s-disease
#17
Rocio Gomez-Pastor, Eileen T Burchfiel, Daniel W Neef, Alex M Jaeger, Elisa Cabiscol, Spencer U McKinstry, Argenia Doss, Alejandro Aballay, Donald C Lo, Sergey S Akimov, Christopher A Ross, Cagla Eroglu, Dennis J Thiele
Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defects caused by protein misfolding. We report that HSF1 is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human HD iPSCs and in brain samples from patients with HD...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28149200/microrna-32-promotes-cell-proliferation-migration-and-suppresses-apoptosis-in-breast-cancer-cells-by-targeting-fbxw7
#18
Wei Xia, JueYu Zhou, HaiBo Luo, YunZhou Liu, CanCan Peng, WenLing Zheng, WenLi Ma
BACKGROUND: MicroRNAs are a class of small non-coding RNAs that are involved in many important physiological and pathological processes by regulating gene expression negatively. The purpose of this study was to investigate the effect of miR-32 on cell proliferation, migration and apoptosis and to determine the functional connection between miR-32 and FBXW7 in breast cancer. METHODS: In this study, quantitative RT-PCR was used to evaluate the expression levels of miR-32 in 27 breast cancer tissues, adjacent normal breast tissues and human breast cancer cell lines...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28099906/genomic-characteristics-of-pancreatic-squamous-cell-carcinoma-an-investigation-by-using-high-throughput-sequencing-after-in-solution-hybrid-capture
#19
Meng-Dan Xu, Shu-Ling Liu, Yi-Zhong Feng, Qiang Liu, Meng Shen, Qiaoming Zhi, Zeyi Liu, Dong-Mei Gu, Jie Yu, Liu-Mei Shou, Fei-Ran Gong, Qi Zhu, Weiming Duan, Kai Chen, Junning Zhang, Meng-Yao Wu, Min Tao, Wei Li
Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28078112/molecular-spectrum-of-kras-nras-braf-pik3ca-tp53-and-apc-somatic-gene-mutations-in-arab-patients-with-colorectal-cancer-determination-of-frequency-and-distribution-pattern
#20
Humaid O Al-Shamsi, Jeremy Jones, Yazan Fahmawi, Ibrahim Dahbour, Aziz Tabash, Reham Abdel-Wahab, Ahmed O S Abousamra, Kenna R Shaw, Lianchun Xiao, Manal M Hassan, Benjamin R Kipp, Scott Kopetz, Amr S Soliman, Robert R McWilliams, Robert A Wolff
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed...
December 2016: Journal of Gastrointestinal Oncology
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