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https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#1
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#2
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445985/interleukin-22-promotes-aerobic-glycolysis-associated-with-tumor-progression-via-targeting-hexokinase-2-in-human-colon-cancer-cells
#3
Yulin Liu, Fan Xiang, Yongming Huang, Liang Shi, Chaojie Hu, Yiming Yang, Di Wang, Nan He, Kaixiong Tao, Ke Wu, Guobin Wang
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#4
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445977/serglycin-as-a-potential-biomarker-for-glioma-association-of-serglycin-expression-extent-of-mast-cell-recruitment-and-glioblastoma-progression
#5
Ananya Roy, Sanaz Attarha, Holger Weishaupt, Per-Henrik Edqvist, Fredrik J Swartling, Michael Bergqvist, Florian A Siebzehnrubl, Anja Smits, Fredrik Pontén, Elena Tchougounova
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445974/lowered-expression-of-microrna-125a-5p-in-human-hepatocellular-carcinoma-and-up-regulation-of-its-oncogenic-targets-sirtuin-7-matrix-metalloproteinase-11-and-c-raf
#6
Nicola Coppola, Giorgio de Stefano, Marta Panella, Lorenzo Onorato, Valentina Iodice, Carmine Minichini, Nicola Mosca, Luisa Desiato, Nunzia Farella, Mario Starace, Giulia Liorre, Nicoletta Potenza, Evangelista Sagnelli, Aniello Russo
Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445967/lactobacillus-casei-zhang-and-vitamin-k2-prevent-intestinal-tumorigenesis-in-mice-via-adiponectin-elevated-different-signaling-pathways
#7
Yong Zhang, Chen Ma, Jie Zhao, Haiyan Xu, Qiangchuan Hou, Heping Zhang
The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445956/rhbdd1-upregulates-egfr-via-the-ap-1-pathway-in-colorectal-cancer
#8
Fei Miao, Mengmeng Zhang, Yuechao Zhao, Xiaolu Li, Rongyan Yao, Fan Wu, Rong Huang, Kai Li, Shiying Miao, Changwu Ma, Hongge Ju, Wei Song, Linfang Wang
Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to promote colorectal cancer growth. In the present study, EGFR was decreased when RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells. c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored EGFR expression, but this effect was counteracted by c-Jun knockdown...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445954/a-clinically-feasible-multiplex-proteomic-immunoassay-as-a-novel-functional-diagnostic-for-pancreatic-ductal-adenocarcinoma
#9
Kian-Huat Lim, Emma Langley, Feng Gao, Jingqin Luo, Lin Li, Gary Meyer, Phillip Kim, Sharat Singh, Vladamir M Kushnir, Dayna S Early, Daniel K Mullady, Steven A Edmundowicz, Sachin Wani, Faris M Murad, Dengfeng Cao, Riad R Azar, Andrea Wang-Gillam
To date, targeted therapy for pancreatic ductal adenocarcinoma (PDAC) remains largely unsuccessful in the clinic. Current genomics-based technologies are unable to reflect the quantitative, dynamic signaling changes in the tumor, and require larger tumor samples that are difficult to obtain in PDAC patients. Therefore, a highly sensitive functional tool that can reliably and comprehensively inform intra-tumoral signaling events is direly needed to guide treatment decision. We tested the utility of a highly sensitive proteomics-based functional diagnostic platform, Collaborative Enzyme Enhanced Reactive-immunoassay (CEERTM), on fine-needle aspiration (FNA) samples obtained from 102 patients with radiographically-evident pancreatic tumors...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445953/yeats4-promotes-the-tumorigenesis-of-pancreatic-cancer-by-activating-beta-catenin-tcf-signaling
#10
Chen Jixiang, Dang Shengchun, Qu Jianguo, Mao Zhengfa, Fan Xin, Wang Xuqing, Zhang Jianxin, Cui Lei
Beta-catenin/TCF signaling has been reported to promote the growth and metastasis of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF transcriptional complex remains largely unknown. Here, we have found that YEATS4 is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4 was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse model. Up-regulation of YEATS4 promoted the growth, migration and invasion of pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited the growth, migration, invasion and metastasis of pancreatic cancer cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445950/the-discovery-of-a-novel-compound-with-potent-antitumor-activity-virtual-screening-synthesis-biological-evaluation-and-preliminary-mechanism-study
#11
Yuanyuan Jin, Linhu Li, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Weiyi Shen
Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC50s: 6.92-8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#12
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#13
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#14
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445934/jarid2-is-essential-for-the-maintenance-of-tumor-initiating-cells-in-bladder-cancer
#15
Xin-Xing Zhu, Ya-Wei Yan, Chun-Zhi Ai, Shan Jiang, Shan-Shan Xu, Min Niu, Xiang-Zhen Wang, Gen-Shen Zhong, Xi-Feng Lu, Yu Xue, Shaoqi Tian, Guangyao Li, Shaojun Tang, Yi-Zhou Jiang
Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445813/microfluidic-integrated-patterned-ito-immunosensor-for-rapid-detection-of-prostate-specific-membrane-antigen-biomarker-in-prostate-cancer
#16
Rajesh Seenivasan, Chandra K Singh, Jay W Warrick, Nihal Ahmad, Sundaram Gunasekaran
An optically transparent patterned indium tin oxide (ITO) three-electrode sensor integrated with a microfluidic channel was designed for label-free immunosensing of prostate-specific membrane antigen (PSMA), a prostate cancer (PCa) biomarker, expressed on prostate tissue and circulating tumor cells but also found in serum. The sensor relies on cysteamine capped gold nanoparticles (N-AuNPs) covalently linked with anti-PSMA antibody (Ab) for target specificity. A polydimethylsiloxane (PDMS) microfluidic channel is used to efficiently and reproducibly introduce sample containing soluble proteins/cells to the sensor...
April 11, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28445812/portable-aptamer-biosensor-of-platelet-derived-growth-factor-bb-using-a-personal-glucose-meter-with-triply-amplified
#17
Lu Hong, Fu Zhou, Dongmin Shi, Xiaojun Zhang, Guangfeng Wang
Sensitive and rapid detection of platelet-derived growth factor BB (PDGF-BB), a cancer-related protein, could help early diagnosis, treatment, and prognosis of cancers. Although some methods have been developed to detect PDGF-BB, few can provide quantitative results using an affordable and portable device that is suitable for home use or field application. In this work, we report the first use of a portable kind of personal glucose meter (PGM) combining a catalytic and molecular beacon (CAMB) system with a cation exchange reaction (CX reaction) for ultrasensitive PDGF-BB assay...
April 19, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28445781/mitochondrial-ros-control-of-cancer
#18
REVIEW
María Del Pilar Sosa Idelchik, Ulrike Begley, Thomas J Begley, J Andrés Melendez
Mitochondria serve a primary role in energy maintenance but also function to govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have long been established to play a critical role in tumorigenesis and are now considered to be integral to the regulation of diverse signaling networks that drive proliferation, tumor cell survival and malignant progression. mROS can damage DNA, activate oncogenes, block the function of tumor suppressors and drive migratory signaling. The mitochondrion's oxidant scavenging systems including SOD2, Grx2, GPrx, Trx and TrxR are key of the cellular redox tone...
April 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#19
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#20
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
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