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Oncogenesis

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https://www.readbyqxmd.com/read/28194033/integrative-analyses-of-transcriptome-sequencing-identify-novel-functional-lncrnas-in-esophageal-squamous-cell-carcinoma
#1
C-Q Li, G-W Huang, Z-Y Wu, Y-J Xu, X-C Li, Y-J Xue, Y Zhu, J-M Zhao, M Li, J Zhang, J-Y Wu, F Lei, Q-Y Wang, S Li, C-P Zheng, B Ai, Z-D Tang, C-C Feng, L-D Liao, S-H Wang, J-H Shen, Y-J Liu, X-F Bai, J-Z He, H-H Cao, B-L Wu, M-R Wang, D-C Lin, H P Koeffler, L-D Wang, X Li, E-M Li, L-Y Xu
Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC...
February 13, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28134937/platelet-activating-factor-paf-receptor-as-a-promising-target-for-cancer-cell-repopulation-after-radiotherapy
#2
I A da Silva-Jr, R Chammas, A P Lepique, S Jancar
A major drawback of radiotherapy is the accelerated growth of the surviving tumor cells. Radiotherapy generates a variety of lipids that bind to the receptor for platelet-activating factor, expressed by cells in the tumor microenvironment. In the present study, using the TC-1 tumor cell line, we found that irradiation induced a twofold increase in receptor expression and generated agonists of receptor. Irradiated cells induced a 20-fold increase in live TC-1 proliferation in vitro. Furthermore, subcutaneous co-injection of irradiated TC-1 cells with TC-1 expressing luciferase (TC-1 fluc(+)) markedly increased TC-1 fluc(+) proliferation in a receptor-dependent way...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28134936/hepatocyte-specific-smad7-deletion-accelerates-den-induced-hcc-via-activation-of-stat3-signaling-in-mice
#3
T Feng, J Dzieran, X Yuan, A Dropmann, T Maass, A Teufel, S Marhenke, T Gaiser, F Rückert, I Kleiter, S Kanzler, M P Ebert, A Vogel, P Ten Dijke, S Dooley, N M Meindl-Beinker
TGF-β signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-β signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28134935/egr-1-regulates-irradiation-induced-autophagy-through-atg4b-to-promote-radioresistance-in-hepatocellular-carcinoma-cells
#4
W-X Peng, Y-Y Wan, A-H Gong, L Ge, J Jin, M Xu, C-Y Wu
Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28134934/ck2-abrogates-the-inhibitory-effects-of-prh-hhex-on-prostate-cancer-cell-migration-and-invasion-and-acts-through-prh-to-control-cell-proliferation
#5
Y H Siddiqui, R M Kershaw, E H Humphreys, E M Assis Junior, S Chaudhri, P-S Jayaraman, K Gaston
PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28134933/inhibition-of-the-integrin-fak-signaling-axis-and-c-myc-synergistically-disrupts-ovarian-cancer-malignancy
#6
B Xu, J Lefringhouse, Z Liu, D West, L A Baldwin, C Ou, L Chen, D Napier, L Chaiswing, L D Brewer, D St Clair, O Thibault, J R van Nagell, B P Zhou, R Drapkin, J-A Huang, M L Lu, F R Ueland, X H Yang
Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28112720/long-noncoding-rna-hoxa-as2-represses-p21-and-klf2-expression-transcription-by-binding-with-ezh2-lsd1-in-colorectal-cancer
#7
J Ding, M Xie, Y Lian, Y Zhu, P Peng, J Wang, L Wang, K Wang
Long noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a transcription level. HOXA-AS2 is previously found to be overexpressed in gastric cancer (GC) and promotes GC cells proliferation. However, its potential role and molecular mechanism in colorectal cancer (CRC) are not known...
January 23, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28112719/the-role-of-the-cancer-stem-cell-marker-cd271-in-dna-damage-response-and-drug-resistance-of-melanoma-cells
#8
T Redmer, I Walz, B Klinger, S Khouja, Y Welte, R Schäfer, C Regenbrecht
Several lines of evidence have suggested that stemness and acquired resistance to targeted inhibitors or chemotherapeutics are mechanistically linked. Here we observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was increased in drug-sensitive cells but not resistant cells in response to DNA-damaging chemotherapeutics etoposide, fotemustine and cisplatin. Comparative analysis of melanoma cells engineered to stably express CD271 or a targeting short hairpin RNA by expression profiling provided numerous genes regulated in a CD271-dependent manner...
January 23, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28092370/api5-confers-cancer-stem-cell-like-properties-through-the-fgf2-nanog-axis
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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