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Oncogenesis

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https://www.readbyqxmd.com/read/28092370/api5-confers-cancer-stem-cell-like-properties-through-the-fgf2-nanog-axis
#1
K-H Song, H Cho, S Kim, H-J Lee, S J Oh, S R Woo, S-O Hong, H S Jang, K H Noh, C H Choi, J-Y Chung, S M Hewitt, J-H Kim, M Son, S-H Kim, B I Lee, H-C Park, Y-K Bae, T W Kim
Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28092369/context-dependent-role-for-chromatin-remodeling-component-pbrm1-baf180-in-clear-cell-renal-cell-carcinoma
#2
A Murakami, L Wang, S Kalhorn, P Schraml, W K Rathmell, A C Tan, R Nemenoff, K Stenmark, B-H Jiang, M E Reyland, L Heasley, C-J Hu
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein. However, it is unclear how the H1H2 type ccRCC tumors escape HIF1's tumor-suppressive activity. The polybromo-1 (PBRM1) gene coding for the BAF180 protein, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, is inactivated in 40% ccRCCs, the function and mechanism of BAF180 mutation is unknown...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28067907/grhl2-reduces-invasion-and-migration-through-inhibition-of-tgf%C3%AE-induced-emt-in-gastric-cancer
#3
J Xiang, X Fu, W Ran, Z Wang
Metastasis is one of the typical features of malignancy that significantly increases cancer-related mortality. Recent studies have shown that epithelial-mesenchymal transition (EMT) is closely related to the invasion and migration of cancer cells. Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. In the previous study, we have reported that Grhl2 functioned as a tumor suppressor in proliferation and apoptosis of gastric cancer. Here we aim to explore the effects of Grhl2 on invasion and migration of gastric cancer and further clarify its possible underlying mechanisms...
January 9, 2017: Oncogenesis
https://www.readbyqxmd.com/read/27991916/the-hif-phf8-ar-axis-promotes-prostate-cancer-progression
#4
D Tong, Q Liu, G Liu, W Yuan, L Wang, Y Guo, W Lan, D Zhang, S Dong, Y Wang, H Xiao, J Mu, C Mao, J Wong, J Jiang
Recent studies provide strong evidence that the androgen receptor (AR) signaling pathway remains active in castration-resistant prostate cancer (CRPC). However, the underlying mechanisms are not well understood. In this study, we demonstrate that plant homeo domain finger protein 8 (PHF8 )interacts with and functions as an essential histone demethylase activity-dependent AR coactivator. Furthermore, we demonstrate that the expression of PHF8 is induced by hypoxia in various prostate cancer cell lines. Knockdown of either hypoxia-inducible factor HIF2α or HIF1α almost completely abolished hypoxia-induced PHF8 expression...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27991915/klf4-functions-as-an-activator-of-the-androgen-receptor-through-reciprocal-feedback
#5
M-K Siu, F Suau, W-Y Chen, Y-C Tsai, H-Y Tsai, H-L Yeh, Y-N Liu
In prostate cancer, Krüppel-like factor 4 (KLF4) depletion occurs frequently, suggesting a role as suppressor tumor. KLF4 is a transcription factor associated with androgen receptor (AR) expression; however, its cellular functions and signaling regulation mechanism remain largely unknown. In this study, we demonstrated that activated AR binds to the KLF4 promoter and enhances KLF4 expression, which reciprocally targets the AR promoter, thus sustaining KLF4 activity. Ectopic KLF4 expression in androgen-independent prostate cancer cells induced AR expression and decreased cell proliferation, invasion and bone metastasis...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27991914/the-spliceosome-u2-snrnp-factors-promote-genome-stability-through-distinct-mechanisms-transcription-of-repair-factors-and-r-loop-processing
#6
M Tanikawa, K Sanjiv, T Helleday, P Herr, O Mortusewicz
Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27991913/linking-genomic-reorganization-to-tumor-initiation-via-the-giant-cell-cycle
#7
N Niu, J Zhang, N Zhang, I Mercado-Uribe, F Tao, Z Han, S Pathak, A S Multani, J Kuang, J Yao, R C Bast, A K Sood, M-C Hung, J Liu
To investigate the mechanisms underlying our recent paradoxical finding that mitotically incapacitated and genomically unstable polyploid giant cancer cells (PGCCs) are capable of tumor initiation, we labeled ovarian cancer cells with α-tubulin fused to green fluorescent protein, histone-2B fused to red fluorescent protein and FUCCI (fluorescent ubiquitination cell cycle indicator), and tracked the spatial and time-dependent change in spindle and chromosomal dynamics of PGCCs using live-cell fluorescence time-lapse recording...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27941932/sharpin-promotes-hepatocellular-carcinoma-progression-via-transactivation-of-versican-expression
#8
Y Tanaka, K Tateishi, T Nakatsuka, Y Kudo, R Takahashi, K Miyabayashi, K Yamamoto, Y Asaoka, H Ijichi, R Tateishi, J Shibahara, M Fukayama, T Ishizawa, K Hasegawa, N Kokudo, K Koike
Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel mechanisms of HCC progression through Sharpin overexpression...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27941931/in-vivo-functional-dissection-of-a-context-dependent-role-for-hif1%C3%AE-in-pancreatic-tumorigenesis
#9
T Cheng, Z Jian, K Li, S Raulefs, I Regel, S Shen, X Zou, J Ruland, G O Ceyhan, H Friess, C W Michalski, J Kleeff, B Kong
Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27941930/erk-mediated-nf-%C3%AE%C2%BAb-activation-through-asic1-in-response-to-acidosis
#10
B Chen, J Liu, T-T Ho, X Ding, Y-Y Mo
Acidic microenvironment is a common feature of solid tumors. We have previously shown that neuron specific acid-sensing ion channel 1 (ASIC1) is expressed in breast cancer, and it is responsible for acidosis-induced cellular signaling through AKT, leading to nuclear factor-κB (NF-κB) activation, and cell invasion and metastasis. However, AKT is frequently activated in cancer. Thus, a key question is whether ASIC1-mediated cell signaling still takes place in the cancer cells carrying constitutively active AKT...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27918553/jagged-1-is-a-major-notch-ligand-along-cholangiocarcinoma-development-in-mice-and-humans
#11
L Che, B Fan, M G Pilo, Z Xu, Y Liu, A Cigliano, A Cossu, G Palmieri, R M Pascale, A Porcu, G Vidili, M Serra, F Dombrowski, S Ribback, D F Calvisi, X Chen
Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27918552/hmyh-and-hmth1-cooperate-for-survival-in-mismatch-repair-defective-t-cell-acute-lymphoblastic-leukemia
#12
S Eshtad, Z Mavajian, S G Rudd, T Visnes, J Boström, M Altun, T Helleday
hMTH1 is an 8-oxodGTPase that prevents mis-incorporation of free oxidized nucleotides into genomic DNA. Base excision and mismatch repair pathways also restrict the accumulation of oxidized lesions in DNA by removing the mis-inserted 8-oxo-7,8-dihydro-2'-deoxyguanosines (8-oxodGs). In this study, we aimed to investigate the interplay between hMYH DNA glycosylase and hMTH1 for cancer cell survival by using mismatch repair defective T-cell acute lymphoblastic leukemia (T-ALL) cells. To this end, MYH and MTH1 were silenced individually or simultaneously using small hairpin RNAs...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27918551/hepatocarcinogenesis-in-transgenic-mice-carrying-hepatitis-b-virus-pre-s-s-gene-with-the-sw172-mutation
#13
M-W Lai, K-H Liang, W-R Lin, Y-H Huang, S-F Huang, T-C Chen, C-T Yeh
Hepatitis B virus (HBV) carrying the rtA181T/sW172* mutation conferred cross-resistance to adefovir and lamivudine. Cell-based and clinical studies indicated that HBV carrying this mutation had an increased oncogenic potential. Herein, we created transgenic mouse models to study the oncogenicity of the HBV pre-S/S gene containing this mutation. Transgenic mice were generated by transfer of the HBV pre-S/S gene together with its own promoter into C57B6 mice. Four lines of mice were created. Two of them carried wild-type gene and produced high and low levels of HBV surface antigen (HBsAg) (TgWT-H and L)...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27892920/foxk1-interaction-with-fhl2-promotes-proliferation-invasion-and-metastasis-in-colorectal-cancer
#14
M Wu, J Wang, W Tang, X Zhan, Y Li, Y Peng, X Huang, Y Bai, J Zhao, A Li, C Chen, Y Chen, H Peng, Y Ren, G Li, S Liu, J Wang
The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT-PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays...
November 28, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27869785/classic-il-6r-signalling-is-dispensable-for-intestinal-epithelial-proliferation-and-repair
#15
K Aden, A Breuer, A Rehman, H Geese, F Tran, J Sommer, G H Waetzig, T M Reinheimer, S Schreiber, S Rose-John, J Scheller, P Rosenstiel
Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling...
November 21, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27841855/notch3-inhibits-epithelial-mesenchymal-transition-by-activating-kibra-mediated-hippo-yap-signaling-in-breast-cancer-epithelial-cells
#16
X Zhang, X Liu, J Luo, W Xiao, X Ye, M Chen, Y Li, G-J Zhang
Invasion, metastasis and chemoresistance are leading causes of death in breast cancer patients. A vital change of epithelial cells, epithelial-mesenchymal transition (EMT), is involved in these processes. Unfortunately, the molecular mechanisms controlling EMT remain to be elucidated. Our previous studies have shown that ectopic N3ICD expression inhibits EMT in MDA-MB-231, a triple-negative breast cancer (TNBC) epithelial cell line. To decipher the mechanism, we performed in-depth studies. Specifically, we found that overexpressing N3ICD transcriptionally upregulated the expression of Kibra, an upstream member of the Hippo pathway...
November 14, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27819668/sall4-promotes-gastric-cancer-progression-through-activating-cd44-expression
#17
X Yuan, X Zhang, W Zhang, W Liang, P Zhang, H Shi, B Zhang, M Shao, Y Yan, H Qian, W Xu
The stem cell factor SALL4 (Sal-like protein 4) plays important roles in the development and progression of cancer. SALL4 is critically involved in tumour growth, metastasis and therapy resistance. However, the underlying mechanisms responsible for the oncogenic roles of SALL4 have not been well characterized. In this study, we demonstrated that SALL4 knockdown by short hairpin RNA greatly inhibited the proliferation, migration and invasion of gastric cancer cells. We further confirmed the inhibitory effects of SALL4 knockdown on gastric cancer cells by using a tetracycline-inducible system...
November 7, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27797363/constitutively-activated-pi3k-accelerates-tumor-initiation-and-modifies-histopathology-of-breast-cancer
#18
M R Sheen, J D Marotti, M J Allegrezza, M Rutkowski, J R Conejo-Garcia, S Fiering
The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53(fl/fl) deletion and Kras(G12D) also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner...
October 31, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27775701/gpr133-adgrd1-an-adhesion-g-protein-coupled-receptor-is-necessary-for-glioblastoma-growth
#19
N S Bayin, J D Frenster, J R Kane, J Rubenstein, A S Modrek, R Baitalmal, I Dolgalev, K Rudzenski, L Scarabottolo, D Crespi, L Redaelli, M Snuderl, J G Golfinos, W Doyle, D Pacione, E C Parker, A S Chi, A Heguy, D J MacNeil, N Shohdy, D Zagzag, D G Placantonakis
Glioblastoma (GBM) is a deadly primary brain malignancy with extensive intratumoral hypoxia. Hypoxic regions of GBM contain stem-like cells and are associated with tumor growth and angiogenesis. The molecular mechanisms that regulate tumor growth in hypoxic conditions are incompletely understood. Here, we use primary human tumor biospecimens and cultures to identify GPR133 (ADGRD1), an orphan member of the adhesion family of G-protein-coupled receptors, as a critical regulator of the response to hypoxia and tumor growth in GBM...
October 24, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27775700/axl-egfr-receptor-tyrosine-kinase-hetero-interaction-provides-egfr-with-access-to-pro-invasive-signalling-in-cancer-cells
#20
M Vouri, D R Croucher, S P Kennedy, Q An, G J Pilkington, S Hafizi
Acquired resistance to conventional and targeted therapies is becoming a major hindrance in cancer management. It is increasingly clear that cancer cells are able to evolve and rewire canonical signalling pathways to their advantage, thus evading cell death and promoting cell invasion. The Axl receptor tyrosine kinase (RTK) has been shown to modulate acquired resistance to EGFR-targeted therapies in both breast and lung cancers. Glioblastoma multiforme (GBM) is a highly infiltrative and invasive form of brain tumour with little response to therapy...
October 24, 2016: Oncogenesis
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