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https://www.readbyqxmd.com/read/27926868/cmyc-regulates-the-size-of-the-premigratory-neural-crest-stem-cell-pool
#1
Laura Kerosuo, Marianne E Bronner
The neural crest is a transient embryonic population that originates within the central nervous system (CNS) and then migrates into the periphery and differentiates into multiple cell types. The mechanisms that govern neural crest stem-like characteristics and self-renewal ability are poorly understood. Here, we show that the proto-oncogene cMyc is a critical factor in the chick dorsal neural tube, where it regulates the size of the premigratory neural crest stem cell pool. Loss of cMyc dramatically decreases the number of emigrating neural crest cells due to reduced self-renewal capacity, increased cell death, and shorter duration of the emigration process...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926866/inflammation-induced-oxidative-stress-mediates-gene-fusion-formation-in-prostate-cancer
#2
Ram S Mani, Mohammad A Amin, Xiangyi Li, Shanker Kalyana-Sundaram, Brendan A Veeneman, Lei Wang, Aparna Ghosh, Adam Aslam, Susmita G Ramanand, Bradley J Rabquer, Wataru Kimura, Maxwell Tran, Xuhong Cao, Sameek Roychowdhury, Saravana M Dhanasekaran, Nallasivam Palanisamy, Hesham A Sadek, Payal Kapur, Alisa E Koch, Arul M Chinnaiyan
Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#3
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926786/nut-midline-carcinoma-of-the-larynx-an-international-series-and-review-of-the-literature
#4
Henrik Hellquist, Christopher A French, Justin A Bishop, Andrés Coca-Pelaz, Evan J Propst, António Paiva Correia, Bo-Yee Ngan, Ronald Grant, Nicole A Cipriani, David Vokes, Rui Henrique, Fernando Pardal, Jose Ramon Vizcaino, Alessandra Rinaldo, Alfio Ferlito
AIMS: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that characteristically locates to the midline of the head and neck, and mediastinum. NMC is characterised by chromosomal rearrangements of the gene encoding nuclear protein in testis, NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare and we report a case series of seven cases...
December 7, 2016: Histopathology
https://www.readbyqxmd.com/read/27926533/andrographolide-impedes-cancer-stemness-and-enhances-radio-sensitivity-in-oral-carcinomas-via-mir-218-activation
#5
Po-Yu Yang, Pei-Ling Hsieh, Tong Hong Wang, Cheng-Chia Yu, Ming-Yi Lu, Yi-Wen Liao, Tzu-Hsin Lee, Chih-Yu Peng
Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926513/mael-is-essential-for-cancer-cell-survival-and-tumorigenesis-through-protection-of-genetic-integrity
#6
Su-Hyeon Kim, Eun-Ran Park, Eugene Cho, Won-Hee Jung, Ju-Yeon Jeon, Hyun-Yoo Joo, Kee-Ho Lee, Hyun-Jin Shin
Germ line-specific genes are activated in somatic cells during tumorigenesis, and are accordingly referred to as cancer germline genes. Such genes that act on piRNA (Piwi-interacting RNA) processing play an important role in the progression of cancer cells. Here, we show that the spermatogenic transposon silencer maelstrom (Mael), a piRNA-processing factor, is required for malignant transformation and survival of cancer cells. A specific Mael isoform was distinctively overexpressed in diverse human cancer cell lines and its depletion resulted in cancer-specific cell death, characterized by apoptosis and senescence, accompanied by an increase in reactive oxygen-species and DNA damage...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926512/depression-of-oncogenecity-by-dephosphorylating-and-degrading-bcr-abl
#7
Miao Gao, Zheng-Lan Huang, Kun Tao, Qing Xiao, Xin Wang, Wei-Xi Cao, Min Xu, Jing Hu, Wen-Li Feng
Aberrant phosphorylation and overexpression of BCR-ABL fusion protein are responsible for the main pathogenesis in chronic myeloid leukemia (CML). Phosphorylated BCR-ABL Y177 recruits GRB2 adaptor and triggers leukemic RAS-MAPK and PI3K-AKT signals. In this study, we engineered a SPOA system to dephosphorylate and degrade BCR-ABL by targeting BCR-ABL Y177. We tested its effect on BCR-ABL phosphorylation and expression, as well as cell proliferation and apoptosis in CML cells. We found that SPOA remarkably dephosphorylated BCR-ABL Y177, prevented GRB2 recruitment, and uncoupled RAS-MAPK and PI3K-AKT signals...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926508/microrna-497-inhibits-thyroid-cancer-tumor-growth-and-invasion-by-suppressing-bdnf
#8
Peisong Wang, Xianying Meng, Yan Huang, Zhi Lv, Jia Liu, Guimin Wang, Wei Meng, Shuai Xue, Qiang Zhang, Pengju Zhang, Guang Chen
miR-497 reportedly plays critical roles in tumor development and progression in many types of cancers. We therefore investigated the function and underlying mechanism of miR-497 in thyroid cancer. We found that miR-497 is downregulated in thyroid cancer tissues, and that miR-497 levels are negatively correlated with advanced clinical stage and lymph node metastasis. Overexpressed miR-497 suppressed thyroid cancer cell proliferation, colony formation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926490/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#9
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926480/calcium-dependent-binding-of-myc-to-calmodulin
#10
Philipp Raffeiner, Andrea Schraffl, Thomas Schwarz, Ruth Röck, Karin Ledolter, Markus Hartl, Robert Konrat, Eduard Stefan, Klaus Bister
The bHLH-LZ (basic region/helix-loop-helix/leucine zipper) oncoprotein Myc and the bHLH-LZ protein Max form a binary transcription factor complex controlling fundamental cellular processes. Deregulated Myc expression leads to neoplastic transformation and is a hallmark of most human cancers. The dynamics of Myc transcription factor activity are post-translationally coordinated by defined protein-protein interactions. Here, we present evidence for a second messenger controlled physical interaction between the Ca2+ sensor calmodulin (CaM) and all Myc variants (v-Myc, c-Myc, N-Myc, and L-Myc)...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925213/the-p53-inhibitor-mdm4-cooperates-with-multiple-genetic-lesions-in-tumorigenesis
#11
Shunbin Xiong, Vinod Pant, Yun Zhang, Neeraj K Aryal, M James You, Donna Kusewitt, Guillermina Lozano
The p53 inhibitor Mdm4 is present at high levels in multiple human cancers. Overexpression of Mdm4 in mice drives spontaneous development of mostly lymphomas and sarcomas. In this study, we explored the ability of Mdm4 to cooperate with other lesions in tumour development. The Mdm4 transgene contributed to mammary tumour development in a BALB/cJ background. High levels of Mdm4 enhanced tumour development in a mutant p53R172H heterozygous background and reduced the need to lose the wild type p53 allele as compared to the mice heterozygous only for the p53R172H mutation...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27925194/sv40-infection-of-mesenchymal-stromal-cells-from-wharton-s-jelly-drives-the-production-of-inflammatory-and-tumoral-mediators
#12
Carolina Cason, Giuseppina Campisciano, Nunzia Zanotta, Erica Valencic, Serena Delbue, Ramona Bella, Manola Comar
The Mesenchymal Stromal Cells from umbilical cord Wharton's jelly (WJSCs) are a source of cells with high potentiality for the treatment of human immunological disorders. Footprints of the oncogenic viruses Simian Virus 40 (SV40) and JC Virus (JCPyV) have been recently detected in human WJSCs specimens. The aim of this study is to evaluate if WJSCs can be efficiently infected by these Polyomaviruses and if they can potentially exert tumoral activity. Cell culture experiments indicated that WJSCs could sustain both SV40 and JCPyV infections...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924922/metabolic-adaptation-to-nutritional-stress-in-human-colorectal-cancer
#13
Masaaki Miyo, Masamitsu Konno, Naohiro Nishida, Toshinori Sueda, Kozo Noguchi, Hidetoshi Matsui, Hugh Colvin, Koichi Kawamoto, Jun Koseki, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Noriko Gotoh, Fumio Matsuda, Taroh Satoh, Tsunekazu Mizushima, Hiroshi Shimizu, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924561/detection-and-functional-analysis-of-sumo-modified-mek
#14
Yuji Kubota, Mutsuhiro Takekawa
Small ubiquitin-like modifier (SUMO) is a posttranslational protein modifier that binds target proteins covalently (protein sumoylation) and remarkably alters their functions. Protein sumoylation has been linked to various cellular functions such as cell division, DNA repair, and import of nuclear proteins. Thus, its dysregulation is implicated in diverse human diseases such as neurodegenerative disorders and cancers. We recently found that the kinase activity of MEK proteins, which function as central components of the ERK-MAPK cascade and amplify an extracellular proliferation signal, is negatively regulated by sumoylation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924560/assaying-activation-and-subcellular-localization-of-erk-in-cells-and-tissues
#15
Carme Caelles, Carles Bayod, Melisa Morcillo
The extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are the focus of many studies due to their involvement in numerous physiological and pathological processes, such as cell proliferation and differentiation, and oncogenic transformation, respectively. ERK1/2 belong to the mitogen-activated protein kinase (MAPKs) family, which are serine/threonine kinases that participate in signal transduction and are activated by dual phosphorylation in the Thr-X-Tyr motif located in their activation loop...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924482/identification-of-small-molecule-modulators-of-microrna-by-library-screening
#16
Zhangang Xiao, Yangchao Chen
MicroRNAs (miRNAs) function as oncogenes or tumor suppressors and are dysregulated in cancer. miRNAs therefore represent promising therapeutic targets for cancer. Small molecules that could modulate the expression of miRNAs would thus have potential as anticancer agents. Library screening of small molecules targeting miRNAs is a useful technology platform for anticancer drug development. Here, we describe a hepatocellular carcinoma (HCC) cell-based luciferase reporter system which could be used to screen for small molecule modulators of tumor suppressor microRNA-34a...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924478/evaluating-synergistic-effects-of-mir-34a-mimics-in-combination-with-other-therapeutic-agents-in-cultured-non-small-cell-lung-cancer-cells
#17
Jane Zhao, Andreas G Bader
Tumor suppressor miRNAs such as miR-34a inhibit tumor growth by simultaneously regulating the expression of multiple important oncogenes across multiple oncogenic pathways and, therefore, provide a strong rationale for developing therapeutic miRNA mimics in combination with other therapeutic cancer agents to augment drug sensitivity. Here, we describe the experimental approach for evaluating miRNA and drug combinations using the "fixed ratio" method in cultured non-small cell lung cancer cells.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924072/p53-and-murine-double-mimute-2-mdm2-expression-changes-and-significance-in-different-types-of-endometrial-lesions
#18
Zhongyong Jiang, Wanqing Xu, Gang Dan, Yuan Liu, Jie Xiong
BACKGROUND Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women's health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated...
December 7, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27923993/specific-targeting-of-telomeric-multimeric-g-quadruplexes-by-a-new-triaryl-substituted-imidazole
#19
Ming-Hao Hu, Shuo-Bin Chen, Bo Wang, Tian-Miao Ou, Lian-Quan Gu, Jia-Heng Tan, Zhi-Shu Huang
Multiple G-quadruplex units in the 3'-terminal overhang of human telomeric DNA can associate and form multimeric structures. The specific targeting of such distinctive higher-order G-quadruplexes might be a promising strategy for developing selective anticancer agents with fewer side effects. However, thus far, only a few molecules were found to selectively bind to telomeric multimeric G-quadruplexes, and their effects on cancer cells were unknown. In this study, a new triaryl-substituted imidazole derivative called IZNP-1: was synthesized and found to specifically bind to and strongly stabilize telomeric multimeric G-quadruplexes through intercalating into the pocket between the two quadruplex units...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923688/paraoxonase-3-promotes-cell-proliferation-and-metastasis-by-pi3k-akt-in-oral-squamous-cell-carcinoma
#20
Lili Zhu, Yiyin Shen, Wei Sun
Paraoxonase 3 (PON3) is an oncogene in cancer, however, little is known about the mechanisms and roles of PON3 in oral squamous cell carcinoma (OSCC), which is the aim of our study. We found that the expression of PON3 was up-regulated in OSCC samples and cell lines. PON3 was associated with accelerating cell proliferation, cell cycle, migration and invasion in OSCC cells. Further research showed that PON3 was regulated by PI3K/Akt pathway. We also found that AP-1 was an important transcriptional factor regulating PON3 expression in OSCC...
December 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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