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Carcinogenesis

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https://www.readbyqxmd.com/read/28498896/inhibition-of-prdm14-expression-in-pancreatic-cancer-suppresses-cancer-stem-like-properties-and-liver-metastasis-in-mice
#1
Chiharu Moriya, Hiroaki Taniguchi, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka, Kohzoh Imai
Pancreatic cancer is one of the most lethal types of cancer, with aggressive properties characterized by metastasis, recurrence, and drug resistance. Cancer stem cells are considered to be responsible for these properties. PRDM14, a transcriptional regulator that maintains pluripotency in embryonic stem cells, is overexpressed in some cancers. Here, we assessed PRDM14 expression and the effects of PRDM14 knockdown on cancer stem-like phenotypes in pancreatic cancer. We observed that PRDM14 protein was overexpressed in pancreatic cancer tissues compared with normal pancreatic tissues...
May 12, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28498893/role-of-dhx33-in-c-myc-induced-cancers
#2
Jijun Fu, Yuchu Liu, Xingshun Wang, Baolei Yuan, Yandong Zhang
Oncogene c-Myc is frequently amplified and activated in human cancers. Deregulation of c-Myc protein has been shown to occur in 30% of all human cancers, especially in hematopoietic malignancies. As a transcription factor, c-Myc has been shown to regulate up to 15% of all human genome genes, controlling diverse cellular activities including cell cycle, ribosome biogenesis, protein synthesis, metabolism, apoptosis and angiogenesis. In this report, we provide evidence that the RNA helicase DHX33 is a critical downstream target of c-Myc...
May 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28472347/muc1-knockout-potentiates-murine-lung-carcinogenesis-involving-an-epiregulin-mediated-egfr-activation-feedback-loop
#3
Xiuling Xu, Wenshu Chen, Shuguang Leng, Mabel T Padilla, Bryanna Saxton, Julie Hutt, Mathewos Tessema, Kosuke Kato, Kwang Chul Kim, Steven A Belinsky, Yong Lin
Although MUC1 is believed to be an oncoprotein, this study uncovers cell-type specific functions of MUC1 in the tumor microenvironment. Our results add complexity to the roles of MUC1 in cancer and help to develop intervention approaches against lung cancer.
May 4, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28472268/nickel-induces-transcriptional-down-regulation-of-dna-repair-pathways-in-tumorigenic-and-non-tumorigenic-lung-cells
#4
Susan E Scanlon, Christine D Scanlon, Denise C Hegan, Parker L Sulkowski, Peter M Glazer
The heavy metal nickel is a known carcinogen, and occupational exposure to nickel compounds has been implicated in human lung and nasal cancers. Unlike many other environmental carcinogens, however, nickel does not directly induce DNA mutagenesis, and the mechanism of nickel-related carcinogenesis remains incompletely understood. Cellular nickel exposure leads to signaling pathway activation, transcriptional changes, and epigenetic remodeling, processes also impacted by hypoxia, which itself promotes tumor growth without causing direct DNA damage...
May 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430874/developmental-sall2-transcription-factor-a-new-player-in-cancer
#5
Viviana E Hermosilla, Matias I Hepp, David Escobar, Carlos Farlas, Elizabeth N Riffo, Ariel F Castro, Roxana Pincheira
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers, and is a specific biomarker for Synovial Sarcoma...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430867/emerging-evidence-for-the-role-of-differential-tumor-microenvironment-in-breast-cancer-racial-disparity-a-closer-look-at-the-surroundings
#6
Sachin Kumar Deshmukh, Sanjeev K Srivastava, Nikhil Tyagi, Aamir Ahmad, Ajay P Singh, Ahmed Al Ghadhban, Donna L Dyess, James E Carter, Kari Dugger, Seema Singh
Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28419250/enhanced-glycolysis-regulated-by-hif-1%C3%AE-via-mct-4-promotes-inflammation-in-arsenite-induced-carcinogenesis
#7
Fei Luo, Zhonglan Zou, Xinlu Liu, Min Ling, Qingling Wang, Qi Wang, Lu Lu, Le Shi, Yonglian Liu, Qizhan Liu, Aihua Zhang
Arsenite is well established as a human carcinogen, but the molecular mechanisms leading to arsenite-induced carcinogenesis are complex and elusive. Accelerated glycolysis, a common process in tumor cells called the Warburg effect, is associated with various biological phenomena. However, the role of glycolysis induced by arsenite is unknown. We have found that, with chronic exposure to arsenite, L-02 cells undergo a metabolic shift to glycolysis. In liver cells exposed to arsenite, hypoxia inducible factor-1α (HIF-1α) and monocarboxylate transporter-4 (MCT-4) are over-expressed...
April 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28419191/ppar%C3%AE-promotes-tumor-progression-via-activation-of-glut1-and-slc1-a5-transcription
#8
Wenbo Zhang, Ying Xu, QingGang Xu, Haifeng Shi, Juanjuan Shi, Yongzhong Hou
Malignant cancer cell uncontrolled growth depends on the persistent nutrient availability such as glucose and amino acids, which is required for cancer cell energetic and biosynthetic pathways. As a nuclear hormone receptor, peroxisome-proliferator-activated receptor δ (PPARδ) plays a critical role in inflammation and cancer, however, it is still unclear the regulatory mechanism of PPARδ on cancer cell metabolism. Here we found that PPARδ directly regulated neutral amino acid transporter SLC1-A5 (solutecarrier family 1 member 5) and glucose transporter-1(Glut1) gene transcription, leading to uptake of glucose and amino acid, activation of mTOR signaling, and tumor progression...
April 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28379317/circulating-pancreatic-stellate-stromal-cells-in-pancreatic-cancer-a-fertile-area-for-novel-research
#9
Tony Cy Pang, Zhihong Xu, Srinivasa Pothula, Therese Becker, David Goldstein, Romano C Pirola, Jeremy S Wilson, Minoti V Apte
Pancreatic stellate cells (PSCs) is known to play an important role in facilitating pancreatic cancer progression - both in terms of local tumour growth as well as the establishment of metastases. We have previously demonstrated that PSCs from the primary cancer seed to distant metastatic sites. We therefore hypothesise that PSCs circulate along with pancreatic cancer cells (circulating tumour cells - CTCs) to help create a growth permissive microenvironment at distant metastatic sites. This review aims to explore the concept of circulating PSCs in pancreatic cancer and suggests future directions for research in this area...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28402394/autophagy-and-trkc-nt-3-signaling-joined-forces-boost-the-hypoxic-glioblastoma-cell-survival
#10
Soha Jawhari, Barbara Bessette, Sophie Hombourger, Karine Durand, Aurélie Lacroix, François Labrousse, Marie-Odile Jauberteau, Marie-Hélène Ratinaud, Mireille Verdier
Glioblastoma multiform (GBM), the most common and aggressive primary brain tumor, is characterized by a high degree of hypoxia and resistance to therapy because of its adaptation capacities, including autophagy and growth factors signaling. In this study, we show an efficient hypoxia-induced survival autophagy in four different GBM cell lines (U87MG, M059K, M059J and LN-18) and an activation of a particular neurotrophin signaling pathway. Indeed, the enhancement of both TrkC and NT-3 was followed by downstream p38MAPK phosphorylation, suggesting the occurrence of a survival autocrine loop...
March 31, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28498946/overexpression-of-rev1-promotes-the-development-of-carcinogen-induced-intestinal-adenomas-via-accumulation-of-point-mutation-and-suppression-of-apoptosis-proportionally-to-the-rev1-expression-level
#11
Megumi Sasatani, Yang Xi, Junko Kajimura, Toshiyuki Kawamura, Jinlian Piao, Yuji Masuda, Hiroaki Honda, Kei Kubo, Takahiro Mikamoto, Hiromitsu Watanabe, Yanbin Xu, Hidehiko Kawai, Tsutomu Shimura, Asao Noda, Kanya Hamasaki, Yoichiro Kusunoki, Elena Karamfilova Zaharieva, Kenji Kamiya
Cancer development often involves mutagenic replication of damaged DNA by the error-prone translesion synthesis (TLS) pathway. Aberrant activation of this pathway plays a role in tumorigenesis by promoting genetic mutations. Rev1 controls the function of the TLS pathway, and Rev1 expression levels are associated with DNA damage induced cytotoxicity and mutagenicity. However, it remains unclear whether deregulated Rev1 expression triggers or promotes tumorigenesis in vivo. In this study, we generated a novel Rev1-overexpressing transgenic (Tg) mouse and characterized its susceptibility to tumorigenesis...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28449079/small-non-coding-rna-and-cancer
#12
Giulia Romano, Dario Veneziano, Mario Acunzo, Carlo M Croce
The ENCODE project has reported that at least 80% of the human genome is biologically active, yet only a small part of human DNA encodes for protein. The massive amount of RNA transcribed but not translated into protein can be classified as housekeeping RNA (such as rRNA, tRNA) and regulatory RNA (such as miRNA, piRNA, lncRNA). Small non-coding RNAs, in particular, have been the focus of many studies in the last 20 years and their fundamental role in many human diseases is currently well established. Inter alia, their role in cancer development and progression, as well as in drug resistance, is being increasingly investigated...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28419251/evaluating-genetic-variants-associated-with-breast-cancer-risk-in-high-and-moderate-penetrance-genes-in-asians
#13
Mi-Ryung Han, Wei Zheng, Qiuyin Cai, Yu-Tang Gao, Ying Zheng, Manjeet K Bolla, Kyriaki Michailidou, Joe Dennis, Qin Wang, Alison M Dunning, Paul Brennan, Shou-Tung Chen, Ji-Yeob Choi, Mikael Hartman, Hidemi Ito, Artitaya Lophatananon, Keitaro Matsuo, Hui Miao, Kenneth Muir, Suleeporn Sangrajrang, Chen-Yang Shen, Soo Hwang Teo, Chiu-Chen Tseng, Anna H Wu, Cheng Har Yip, Daehee Kang, Yong-Bing Xiang, Douglas F Easton, Xiao-Ou Shu, Jirong Long
Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS)...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28383684/functional-variants-in-dcaf4-associated-with-lung-cancer-risk-in-european-populations
#14
Hongliang Liu, Zhensheng Liu, Yanru Wang, Thomas E Stinchcombe, Kouros Owzar, Younghun Han, Rayjean J Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria T Landi, Irene Brüske, Angela Risch, Xifeng Wu, Yuanqing Ye, David C Christiani, Christopher I Amos, Qingyi Wei
Cullin-RING ubiquitin ligases (CRLs) responsible for substrate specificity of ubiquitination play a key role in cell-cycle control and DNA damage response. In this study, we assessed associations between 16 599 SNPs in 115 CRL genes and lung cancer risk by using summary data of six published genome-wide association studies (GWASs) of 12 160 cases and 16 838 cases of European ancestry. As a result, we identified three independent SNPs in DCAF4 (rs117781739, rs12587742 and rs2240980) associated with lung cancer risk (odds ratio = 0...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28383667/inactivation-of-jnk2-as-carcinogenic-factor-in-colitis-associated-and-sporadic-colorectal-carcinogenesis
#15
Wiebke Lessel, Andrew Silver, Doerthe Jechorek, Thomas Guenther, Friedrich-Wilhelm Roehl, Thomas Kalinski, Albert Roessner, Angela Poehlmann-Nitsche
We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28379545/reduced-mrna-expression-of-nucleotide-excision-repair-genes-in-lymphocytes-and-risk-of-squamous-cell-carcinoma-of-the-head-and-neck
#16
Peng Han, Fengqin Gao, Hongliang Liu, Zhensheng Liu, Qiong Shi, Jesse D Troy, Kouros Owzar, Walter Lee, Jose P Zevallos, Erich M Sturgis, Qingyi Wei
Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically significantly lower expression levels of DDB1 and ERCC3 (P = 0...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28379297/human-mitochondrial-pyrroline-5-carboxylate-reductase-1-promotes-invasiveness-and-impacts-survival-in-breast-cancers
#17
Jiefeng Ding, Mei-Ling Kuo, Leila Su, Lijun Xue, Frank Luh, Hang Zhang, Jianghai Wang, Tiffany G Lin, Keqiang Zhang, Peiguo Chu, Shu Zheng, Xiyong Liu, Yun Yen
Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28369244/targeted-sequencing-of-chromosome-15q25-identified-novel-variants-associated-with-risk-of-lung-cancer-and-smoking-behavior-in-chinese
#18
Yang Cheng, Cheng Wang, Meng Zhu, Juncheng Dai, Yuzhuo Wang, Liguo Geng, Zhihua Li, Jiahui Zhang, Hongxia Ma, Guangfu Jin, Dongxin Lin, Zhibin Hu, Hongbing Shen
Previous genome-wide association studies (GWAS) in populations of European descent identified a lung cancer susceptibility locus at 15q25 that was biologically associated with nicotine addiction. However, the allele frequency of susceptibility variants identified in this region varied dramatically across European and Asian populations, suggesting that additional risk single nucleotide polymorphism (SNPs) in Asians need to be identified. Thus, we conducted a fine-mapping study of chromosome 15q25 using targeted resequencing of 200 lung cancer cases and 300 controls of Chinese descent...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28369212/associations-between-single-nucleotide-polymorphisms-in-rybp-and-the-prognosis-of-hepatocellular-carcinoma-in-a-chinese-population
#19
Xiaonian Zhu, Zhigang Wang, Xiaoqiang Qiu, Chao Tan, Hongping Yu, Chunhua Bei, Linyuan Qin, Yuan Ren, Shengkui Tan
Down-regulated RINGl and YYl binding protein (RYBP) is reported to be an independent predictor of a poor prognosis in patients with hepatocellular carcinoma (HCC). However, the genetic association of RYBP polymorphisms with HCC risk and prognosis has not been investigated now. In this study, five RYBP SNPs, rs12956, rs2118593, rs17009699, rs4676875 and rs4532099, were studied from a hospital-based case-control study including 1100 cases (HCC patients) and 1100 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28334277/in-bone-metastasis-mir-34a-5p-absence-inversely-correlates-with-met-expression-while-met-oncogene-is-unaffected-by-mir-34a-5p-in-non-metastatic-and-metastatic-breast-carcinomas
#20
Paola Maroni, Rossella Puglisi, Gianfranco Mattia, Alessandra Carè, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
The highlight of the molecular basis and therapeutic targets of the bone-metastatic process requires the identification of biomarkers of metastasis colonization. Here, we studied miR-34a-5p expression, and Met-receptor expression and localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated in non-metastatic breast carcinoma, intermediate in the adjacent tissue and practically absent in bone metastases, opposite to pair-matched carcinoma...
May 1, 2017: Carcinogenesis
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