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Oncogenesis

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https://www.readbyqxmd.com/read/28737757/non-canonical-wnt-pcp-signalling-in-cancer-fzd6-takes-centre-stage
#1
REVIEW
G Corda, A Sala
Frizzled receptors are the mediators of the wnt canonical and non-canonical pathways, which play fundamental roles in cell differentiation and organism development. A large body of work indicates that dysregulation of wnt signalling is a feature of oncogenic transformation, but most of the studies published so far focus on the assessment of the consequences of aberrations of the canonical pathway in human cancer. In this review, we discuss the emerging role of the wnt non-canonical pathway regulated by frizzled receptor 6 (Fzd6) in the pathogenesis of different types of human malignancies...
July 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28737756/overexpression-of-zinc-finger-protein-687-enhances-tumorigenic-capability-and-promotes-recurrence-of-hepatocellular-carcinoma
#2
T Zhang, Y Huang, W Liu, W Meng, H Zhao, Q Yang, S-J Gu, C-C Xiao, C-C Jia, B Zhang, Y Zou, H-P Li, B-S Fu
Zinc finger protein 687 (ZNF687), identified as a C2H2 zinc finger protein, has been found to be mutated and upregulated in giant cell tumor of bone and acute myeloid leukemia, suggesting an oncogenic role for ZNF687 in cancer. However, the clinical significance and precise role of ZNF687 in cancer progression are largely unknown. Herein, we report that ZNF687 was markedly upregulated in hepatocellular carcinoma (HCC) cell lines and HCC tissues, and was significantly correlated with relapse-free survival in HCC...
July 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28714950/tid1-s-regulates-the-mitochondrial-localization-of-egfr-in-non-small-cell-lung-carcinoma
#3
T-H Wang, Y-H Lin, S-C Yang, P-C Chang, T-Cv Wang, C-Y Chen
The epidermal growth factor receptor (EGFR) is the major driver of non-small cell lung carcinoma (NSCLC). Mitochondrial accumulation of EGFR has been shown to promote metastasis in NSCLC, yet little is known about how the mitochondrial localization of EGFR is regulated. In this work, we show that Tid1 (also known as mitochondrial HSP40) is involved in the mitochondrial localization of EGFR, and that the DnaJ domain of Tid1-S is essential for the Tid1-S-mediated transportation of EGFR into mitochondria. Overexpression of Tid1-S increased the migration and invasion of NSCLC cells cultured in vitro...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28714949/aspartate-%C3%AE-hydroxylase-disrupts-mitochondrial-dna-stability-and-function-in-hepatocellular-carcinoma
#4
C Tang, Y Hou, H Wang, K Wang, H Xiang, X Wan, Y Xia, J Li, W Wei, S Xu, Z Lei, T M Pawlik, H Wang, M Wu, F Shen
The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression of aspartate β-hydroxylase (ASPH) in HCC tissues, which was associated with tumor invasiveness and a worse prognosis. Currently, we unexpectedly observed the presence of ASPH in purified mitochondrial protein fraction. In addition, immunostaining of both exogenously and endogenously expressed ASPH showed a colocalization with mitochondrial biomarkers...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692037/srgn-tgf%C3%AE-2-regulatory-loop-confers-invasion-and-metastasis-in-triple-negative-breast-cancer
#5
Z Zhang, Y Deng, G Zheng, X Jia, Y Xiong, K Luo, Q Qiu, Ni Qiu, J Yin, M Lu, H Liu, Y Gu, Z He
Patients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692036/neoadjuvant-chemotherapy-affects-molecular-classification-of-colorectal-tumors
#6
K Trumpi, I Ubink, A Trinh, M Djafarihamedani, J M Jongen, K M Govaert, S G Elias, S R van Hooff, J P Medema, M M Lacle, L Vermeulen, I H M Borel Rinkes, O Kranenburg
The recent discovery of 'molecular subtypes' in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692035/role-of-integrin-linked-kinase-in-regulating-the-protein-stability-of-the-muc1-c-oncoprotein-in-pancreatic-cancer-cells
#7
H-L Huang, H-Y Wu, P-C Chu, I-L Lai, P-H Huang, S K Kulp, S-L Pan, C-M Teng, C-S Chen
MUC1-C overexpression has been associated with the progression of pancreatic tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3 target gene, STAT3 plays a major role in regulating MUC1-C expression. In this study, we report an alternative mechanism by which integrin-linked kinase (ILK) post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. We found that ILK acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692034/mir-200b-inhibits-proliferation-and-metastasis-of-breast-cancer-by-targeting-fucosyltransferase-iv-and-%C3%AE-1-3-fucosylated-glycans
#8
Q Zheng, X Cui, D Zhang, Y Yang, X Yan, M Liu, B Niang, F Aziz, S Liu, Q Yan, J Liu
Aberrant protein fucosylation is associated with cancer malignancy. Fucosyltransferase IV (FUT4) is the key enzyme catalyzing the biosynthesis of α1,3-linkage fucosylated glycans carried by glycoproteins on the cell surface, such as the tumor-associated sugar antigen Lewis Y (LeY). An abnormal increase in the levels of FUT4 and LeY is observed in many cancers and correlated with cell proliferation and metastasis. Some microRNAs (miRNAs) are known to negatively regulate gene expression. FUT4 is an oncogenic glycogene, and thus it is important to identify the specific miRNA targeting FUT4...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692033/spontaneous-loss-of-b-lineage-transcription-factors-leads-to-pre-b-leukemia-in-ebf1-bcl-xl-tg-mice
#9
J A Ramírez-Komo, M A Delaney, D Straign, K Lukin, M Tsang, B M Iritani, J Hagman
Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1(+/-)Bcl-xL(Tg) mice, which express the anti-apoptotic factor Bcl-xL in B cells...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28692032/epigenetic-silencing-of-microrna-137-enhances-asct2-expression-and-tumor-glutamine-metabolism
#10
J Dong, D Xiao, Z Zhao, P Ren, C Li, Y Hu, J Shi, H Su, L Wang, H Liu, B Li, P Gao, G Qing
Tumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28671677/effects-of-proton-versus-photon-irradiation-on-lymph-angiogenic-inflammatory-proliferative-and-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#11
M Lupu-Plesu, A Claren, S Martial, P-D N'Diaye, K Lebrigand, N Pons, D Ambrosetti, I Peyrottes, J Feuillade, J Hérault, M Dufies, J Doyen, G Pagès
The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28671676/jwa-regulates-trail-induced-apoptosis-via-march8-mediated-dr4-ubiquitination-in-cisplatin-resistant-gastric-cancer-cells
#12
Q Wang, Q Chen, L Zhu, M Chen, W Xu, S Panday, Z Wang, A Li, O D Røe, R Chen, S Wang, R Zhang, J Zhou
Platinum chemotherapeutics are widely used to treat solid malignant tumors, including gastric cancer (GC). Drug resistance to platinum compounds may result in cancer relapse and decreased survival. The identification and development of novel agents to reactivate apoptosis pathways in platinum-resistant cancer cells is therefore necessary. Here we report that cisplatin-resistant human GC cells (BGC823/DDP and SGC7901/DDP) but not their parental cells (BGC823 and SGC7901) exhibit high sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a result of overexpression of death receptor 4 (DR4)...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28671675/matrix-stiffness-induces-epithelial-mesenchymal-transition-and-promotes-chemoresistance-in-pancreatic-cancer-cells
#13
A J Rice, E Cortes, D Lachowski, B C H Cheung, S A Karim, J P Morton, A Del Río Hernández
Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28650446/exosomes-from-plasmodium-infected-hosts-inhibit-tumor-angiogenesis-in-a-murine-lewis-lung-cancer-model
#14
Y Yang, Q Liu, J Lu, D Adah, S Yu, S Zhao, Y Yao, L Qin, L Qin, X Chen
Previous research to investigate the interaction between malaria infection and tumor progression has revealed that malaria infection can potentiate host immune response against tumor in tumor-bearing mice. Exosomes may play key roles in disseminating pathogenic host-derived molecules during infection because several studies have shown the involvement and roles of extracellular vesicles in cell-cell communication. However, the role of exosomes generated during Plasmodium infection in tumor growth, progression and angiogenesis has not been studied either in animals or in the clinics...
June 26, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28650445/a-distinct-function-of-the-retinoblastoma-protein-in-the-control-of-lipid-composition-identified-by-lipidomic-profiling
#15
H Muranaka, A Hayashi, K Minami, S Kitajima, S Kohno, Y Nishimoto, N Nagatani, M Suzuki, L A N Kulathunga, N Sasaki, N Okada, T Matsuzaka, H Shimano, H Tada, C Takahashi
Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length...
June 26, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604766/the-deubiquitinating-enzymes-usp4-and-usp17-target-hyaluronan-synthase-2-and-differentially-affect-its-function
#16
M Mehić, V K de Sa, S Hebestreit, C-H Heldin, P Heldin
The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604765/mlk3-regulates-fra-1-and-mmps-to-drive-invasion-and-transendothelial-migration-in-triple-negative-breast-cancer-cells
#17
C Rattanasinchai, B J Llewellyn, S E Conrad, K A Gallo
Mixed-lineage kinase 3 (MLK3), a mitogen-activated protein kinase kinase kinase (MAP3K), has critical roles in metastasis of triple-negative breast cancer (TNBC), in part by regulating paxillin phosphorylation and focal adhesion turnover. However the mechanisms and the distinct step(s) of the metastatic processes through which MLK3 exerts its influence are not fully understood. Here we report that in non-metastatic, estrogen receptor-positive breast cancer (ER+ BC) cells, induced MLK3 expression robustly upregulates the oncogenic transcription factor, FOS-related antigen-1 (FRA-1), which is accompanied by elevation of matrix metalloproteinases (MMPs), MMP-1 and MMP-9...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604764/limited-nucleotide-pools-restrict-epstein-barr-virus-mediated-b-cell-immortalization
#18
A Y Hafez, J E Messinger, K McFadden, G Fenyofalvi, C N Shepard, G M Lenzi, B Kim, M A Luftig
Activation of cellular oncogenes as well as infection with tumor viruses can promote aberrant proliferation and activation of the host DNA damage response. Epstein-Barr virus (EBV) infection of primary human B cells induces a transient period of hyper-proliferation, but many of these infected cells succumb to an ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/Chk2)-mediated senescence-like growth arrest. In this study, we assessed the role of DNA replicative stress and nucleotide pool levels in limiting EBV-infected B-cell outgrowth...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604763/proline-rich-homeodomain-protein-prh-hhex-is-a-suppressor-of-breast-tumour-growth
#19
R M Kershaw, D Roberts, J Wragg, A M Shaaban, E Humphreys, J Halsall, L Price, R Bicknell, K Gaston, P-S Jayaraman
Breast tumours progress from hyperplasia to ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) is a transcription factor that displays both tumour suppressor and oncogenic activity in different disease contexts; however, the role of PRH in breast cancer is poorly understood. Here we show that nuclear localization of the PRH protein is decreased in DCIS and IBC compared with normal breast. Our previous work has shown that PRH phosphorylation by protein kinase CK2 prevents PRH from binding to DNA and regulating the transcription of multiple genes encoding growth factors and growth factor receptors...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604762/tip30-regulates-lipid-metabolism-in-hepatocellular-carcinoma-by-regulating-srebp1-through-the-akt-mtor-signaling-pathway
#20
F Yin, G Sharen, F Yuan, Y Peng, R Chen, X Zhou, H Wei, B Li, W Jing, J Zhao
Lipid reprogramming has been considered as a crucial characteristic in hepatocellular carcinoma (HCC) initiation and progression. However, detailed molecular mechanisms have yet to be clearly defined. Here, we examined the effects of tumor suppressor TIP30 on the regulation of HCC lipid metabolism. We found that decreased TIP30 expression leads to elevated fatty acid synthesis and enhanced levels of lipogenic enzymes SCD and FASN in HCC cells. Moreover, SREBP1 is one of the key transcription factors regulating liver lipid metabolism, and TIP30 deficiency significantly increased SREBP1 expression and nuclear accumulation...
June 12, 2017: Oncogenesis
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