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Oncogenesis

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https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#1
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530705/ccn5-wisp-2-restores-er-%C3%A2-in-normal-and-neoplastic-breast-cells-and-sensitizes-triple-negative-breast-cancer-cells-to-tamoxifen
#2
S Sarkar, A Ghosh, S Banerjee, G Maity, A Das, M A Larson, V Gupta, I Haque, O Tawfik, S K Banerjee
CCN5/WISP-2 is an anti-invasive molecule and prevents breast cancer (BC) progression. However, it is not well understood how CCN5 prevents invasive phenotypes of BC cells. CCN5 protein expression is detected in estrogen receptor-α (ER-α) -positive normal breast epithelial cells as well as BC cells, which are weakly invasive and rarely metastasize depending on the functional status of ER-α. A unique molecular relation between CCN5 and ER-α has been established as the components of the same signaling pathway that coordinate some essential signals associated with the proliferation as well as delaying the disease progression from a non-invasive to invasive phenotypes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530704/upregulation-of-cyp17a1-by-sp1-mediated-dna-demethylation-confers-temozolomide-resistance-through-dhea-mediated-protection-in-glioma
#3
J-Y Chuang, W-L Lo, C-Y Ko, S-Y Chou, R-M Chen, K-Y Chang, J-J Hung, W-C Su, W-C Chang, T-I Hsu
Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530703/trpv4-plays-a-role-in-breast-cancer-cell-migration-via-ca-2-dependent-activation-of-akt-and-downregulation-of-e-cadherin-cell-cortex-protein
#4
W H Lee, L Y Choong, T H Jin, N N Mon, S Chong, C S Liew, T Putti, S Y Lu, C Harteneck, Y P Lim
TRPV4 belongs to the 'Transient Receptor Potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#5
K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra, R V Thakker
Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504694/the-prohibitin-repressive-interaction-with-e2f1-is-rapidly-inhibited-by-androgen-signalling-in-prostate-cancer-cells
#6
S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan, D A Dart
Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#7
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504692/mint3-mediated-l1cam-expression-in-fibroblasts-promotes-cancer-cell-proliferation-via-integrin-%C3%AE-5%C3%AE-1-and-tumour-growth
#8
H J Nakaoka, Z Tanei, T Hara, J S Weng, A Kanamori, T Hayashi, H Sato, A Orimo, K Otsuji, K Tada, T Morikawa, T Sasaki, M Fukayama, M Seiki, Y Murakami, T Sakamoto
Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504691/cxcr3-mediates-ascites-directed-tumor-cell-migration-and-predicts-poor-outcome-in-ovarian-cancer-patients
#9
C Windmüller, D Zech, S Avril, M Boxberg, T Dawidek, B Schmalfeldt, M Schmitt, M Kiechle, H Bronger
Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian cancer (EOC), but the underlying mechanisms have not been fully elucidated. The CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites, but its role in ovarian cancer metastasis is largely unknown. Herein, we first screened two independent cohorts of high-grade serous ovarian cancers (HGSCs, discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3 expression. In primary tumors, CXCR3 was particularly overexpressed by tumor cells at the invasive front...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504690/microrna-645-is-an-oncogenic-regulator-in-colon-cancer
#10
S T Guo, X Y Guo, J Wang, C Y Wang, R H Yang, F H Wang, X Y Li, H Hondermarck, R F Thorne, Y F Wang, L Jin, X D Zhang, C C Jiang
Despite advances in early diagnosis and the development of molecularly targeted therapy, curative treatment of colon cancer once it has metastasized is yet to be accomplished. This is closely associated with deregulated CRC cell proliferation and resistance to apoptosis. Here we reveal that upregulation of microRNA-645 (miR-645) through DNA copy number gain is responsible for enhanced proliferation and resistance to apoptosis in colon cancer. MiR-645 was upregulated in most colon cancer tissues related to adjacent normal mucosa...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504689/molecular-signaling-in-multiple-myeloma-association-of-ras-raf-mutations-and-mek-erk-pathway-activation
#11
J Xu, N Pfarr, V Endris, E K Mai, N H Md Hanafiah, N Lehners, R Penzel, W Weichert, A D Ho, P Schirmacher, H Goldschmidt, M Andrulis, M S Raab
Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be incurable in most cases. A dominant mutation cluster has been identified in RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK signaling as a therapeutic target. As yet, however, the clinical relevance of this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK pathway activation by both targeted sequencing and phospho-ERK immunohistochemistry in 180 tissue biopsies from 103 patients with newly diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM)...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28481368/regulation-of-mir-483-3p-by-the-o-linked-n-acetylglucosamine-transferase-links-chemosensitivity-to-glucose-metabolism-in-liver-cancer-cells
#12
F Pepe, S Pagotto, S Soliman, C Rossi, P Lanuti, C Braconi, R Mariani-Costantini, R Visone, A Veronese
The miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3/PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28481367/inhibition-of-malic-enzyme-1-disrupts-cellular-metabolism-and-leads-to-vulnerability-in-cancer-cells-in-glucose-restricted-conditions
#13
S Murai, A Ando, S Ebara, M Hirayama, Y Satomi, T Hara
Malic enzyme 1 (ME1) regulates one of the main pathways that provide nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for cancer cell growth through maintenance of redox balance and biosynthesis processes in the cytoplasm. In this study, we found that ME1 inhibition disrupted metabolism in cancer cells and inhibited cancer cell growth by inducing senescence or apoptosis. In glucose-restricted culture conditions, cancer cells increased ME1 expression, and tracer experiments with labelled glutamine revealed that the flux of ME1-derived pyruvate to citrate was enhanced...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28481366/the-zinc-finger-transcriptional-factor-slug-transcriptionally-downregulates-er%C3%AE-by-recruiting-lysine-specific-demethylase-1-in-human-breast-cancer
#14
J-W Bai, M-N Chen, X-L Wei, Y-Ch Li, H-Y Lin, M Chen, J-W Li, C-W Du, K Man, G-J Zhang
Estrogen receptor α (ERα) is related with epithelial-mesenchymal transition, invasion and metastasis, and serves as an important therapeutic predictor and prognostic factor in breast cancer patients. The triple negative breast cancer (TNBC) is characterized by loss of hormone receptors and human epidermal growth factor receptor 2 (Her2), and lacks effective targeted therapy with poor prognosis. Unfortunately, the molecular mechanisms of ERα deficiency, which becomes hormone independent and results in resistance to endocrine therapy, remain to be elucidated in breast cancer...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28481365/membrane-bound-%C3%AE-catenin-degradation-is-enhanced-by-ets2-mediated-siah1-induction-in-helicobacter-pylori-infected-gastric-cancer-cells
#15
L Das, S B Kokate, P Dixit, S Rath, N Rout, S P Singh, S E Crowe, A Bhattacharyya
β-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic β-catenin and therefore, impairs nuclear translocation and oncogenic function of β-catenin. However, the effect of Siah1 on the cell membrane bound β-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28459432/metformin-inhibits-suv39h1-mediated-migration-of-prostate-cancer-cells
#16
T Yu, C Wang, J Yang, Y Guo, Y Wu, X Li
Prostate cancer (PCa) is a leading cause of cancer-related death among men, largely due to incurable distant metastases. Metformin, the most common used anti-type-2 diabetes medicine, has been linked to reduced cancer risk and better diagnosis. We found that metformin was able to inhibit PCa cell migration, which correlates with tumor metastatic capability. The pathogenesis and progression of tumors are closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28459431/mirna-34c-5p-inhibits-amphiregulin-induced-ovarian-cancer-stemness-and-drug-resistance-via-downregulation-of-the-areg-egfr-erk-pathway
#17
S-L Tung, W-C Huang, F-C Hsu, Z-P Yang, T-H Jang, J-W Chang, C-M Chuang, C-R Lai, L-H Wang
Epithelial ovarian cancer is the most lethal gynecological cancer mainly due to late diagnosis, easy spreading and rapid development of chemoresistance. Cancer stem cells are considered to be one of the main mechanisms for chemoresistance, as well as metastasis and recurrent disease. To explore the stemness characteristics of ovarian cancer stem cells, we successfully enriched ovarian cancer stem-like cells from an established ovarian cancer cell line (SKOV-I6) and a fresh ovarian tumor-derived cell line (OVS1)...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28436991/crb3-downregulation-confers-breast-cancer-stem-cell-traits-through-taz-%C3%AE-catenin
#18
P Li, Y Wang, X Mao, Y Jiang, J Liu, J Li, J Wang, R Wang, J She, J Zhang, J Yang, Y Liu, P Liu
The cancer stem cell (CSC) theory depicts a special population within the cancer mass that self-renew and sustain the cancer, even if the other cells were eliminated by therapies. How CSCs acquire these unique traits is still unclear. Crumbs homolog 3 (CRB3), a member of the CRB polarity complex, has been reported to act as a tumor suppressor. Here, we detected significantly lower or negative CRB3 expression in human breast cancer tissues. Knockdown of CRB3 generated non-tumorigenic, immortalized breast epithelial cell line MCF 10A with CSC properties...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28436990/tcrp1-promotes-nih-3t3-cell-transformation-by-over-activating-pdk1-and-akt1
#19
C Wang, H Liu, Q Qiu, Z Zhang, Y Gu, Z He
Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28414320/inhibition-of-dna2-nuclease-as-a-therapeutic-strategy-targeting-replication-stress-in-cancer-cells
#20
S Kumar, X Peng, J Daley, L Yang, J Shen, N Nguyen, G Bae, H Niu, Y Peng, H-J Hsieh, L Wang, C Rao, C C Stephan, P Sung, G Ira, G Peng
Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity...
April 17, 2017: Oncogenesis
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