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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/27891679/adenylyl-cyclase-3-adenylyl-cyclase-associated-protein-1-cap1-complex-mediates-the-anti-migratory-effect-of-forskolin-in-pancreatic-cancer-cells
#1
Sierra Quinn, Sarai Graves, Clayton Dains-McGahee, Emilee Friedman, Humma Hassan, Piotr Witkowski, Maria E Sabbatini
Pancreatic cancer is one of the most lethal human malignancies. A better understanding of the intracellular mechanism of migration and invasion is urgently needed to develop treatment that will suppress metastases and improve overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second messenger that has shown to regulate migration and invasion of pancreatic cancer cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the enzyme adenylyl cyclase (AC)...
November 27, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27864909/the-mechanism-of-cirp-in-inhibition-of-keratinocytes-growth-arrest-and-apoptosis-following-low-dose-uvb-radiation
#2
Yi Liao, Jianguo Feng, Yi Zhang, Liling Tang, Shiyong Wu
UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm(2) ), but not high dose (50 mJ/cm(2) ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27864908/e2f-transcription-factor-2-variants-as-predictive-biomarkers-for-recurrence-risk-in-patients-with-squamous-cell-carcinoma-of-the-oropharynx
#3
Yuncheng Li, Erich M Sturgis, Lijun Zhu, Xiaoli Cao, Qingyi Wei, Hua Zhang, Guojun Li
Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1,008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, p < 0...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27864890/anti-egfr-monoclonal-antibodies-enhance-sensitivity-to-dna-damaging-agents-in-brca1-mutated-and-pten-wild-type-triple-negative-breast-cancer-cells
#4
Abderrahim El Guerrab, Mahchid Bamdad, Yves-Jean Bignon, Frédérique Penault-Llorca, Corinne Aubel
Increased epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer (TNBC) is recognized as a promising therapeutic target, specifically through the use of selective EGFR inhibitors combined with chemotherapies. TNBC is characterized by genetic instability that leads to increased sensitivity to cytotoxic agents. We analyzed the effect of anti-EGFR monoclonal antibodies (mAbs; cetuximab and panitumumab) in combination with chemotherapeutic agents (docetaxel, cisplatin and epirubicin) on EGFR-expressing TNBC cell lines that have different mutation statuses for one oncogene (KRAS) and two tumor suppressor genes (PTEN and BRCA1)...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27862371/helicobacter-pylori-infection-modulates-the-expression-of-mirnas-associated-with-dna-mismatch-repair-pathway
#5
Juliana C Santos, Mitsue T Brianti, Victor R Almeida, Manoela M Ortega, Wolfgang Fischer, Rainer Haas, Ander Matheu, Marcelo L Ribeiro
Genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might lead to modifications in cancer-related gene expression and cancer development. Recently, it has been shown that the infection by Helicobacter pylori (H. pylori), the major causative agent of gastric cancer, induces DNA damage and inhibits MMR DNA repair. Also, it has been reported that microRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this study was to identify miRs regulating MMR pathway in H...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27862334/tgf%C3%AE-signaling-confers-sorafenib-resistance-via-induction-of-multiple-rtks-in-hepatocellular-carcinoma-cells
#6
Nathan Ungerleider, Chang Han, Jinqiang Zhang, Lu Yao, Tong Wu
Transforming growth factor β (TGFβ) is a multifunctional cytokine which is importantly implicated in hepatocarcinogenesis. The current study provides novel evidence that TGFβ upregulates the expression of multiple receptor tyrosine kinases (RTKs), including IGF1R, EGFR, PDGFβR, and FGFR1 in human hepatocellular carcinoma (HCC) cells. This, in turn, sensitized HCC cells to individual cognate RTK ligands, leading to cell survival. Our data showed that the TGFβ-mediated increase in growth factor sensitivity led to evasion of apoptosis induced by the mutikinase inhibitor, sorafenib...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27862333/genetic-variants-in-the-promoter-region-of-the-calcium-sensing-receptor-gene-are-associated-with-its-down-regulation-in-neuroblastic-tumors
#7
Laia Masvidal, Raquel Iniesta, Marta García, Carla Casalà, Cinzia Lavarino, Jaume Mora, Carmen de Torres
We have previously reported that the calcium-sensing receptor (CaSR) is expressed in benign, differentiated neuroblastic tumors and epigenetically silenced in undifferentiated, malignant cases. Furthermore, cinacalcet, an allosteric activator of the CaSR, reduces neuroblastoma tumor growth in preclinical models. However, to identify patients that might benefit from this treatment, a complete understanding of mechanisms governing CaSR expression in these tumors would be required. We have now analyzed two polymorphisms in the promoter region of the CASR gene (rs7652589 and rs1501899) by allelic discrimination in neuroblastoma patients and cell lines...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27862321/ptenp1-a-natural-sponge-of-mir-21-mediates-pten-expression-to-inhibit-the-proliferation-of-oral-squamous-cell-carcinoma
#8
Ling Gao, Wenhao Ren, Linmei Zhang, Shaoming Li, Xinjuan Kong, Hao Zhang, Jianwei Dong, Guangfeng Cai, Changxiong Jin, Danqing Zheng, Keqian Zhi
PTENp1, non-coding RNA (ncRNA) pseudogene, is involved in oral squamous cell carcinoma (OSCC). The precise effects mediated by PTENp1 transcripts within intricate regulatory networks involving molecular interactions with ancestral gene PTEN and tumorigenicity in OSCC remain unclear. Here, we found that PTENp1 was aberrantly expressed in OSCC. There was a positive correlation between the expression levels of PTENp1 and PTEN. Further, we showed that PTENp1 acted as a competing endogenous RNA that protects PTEN transcripts from being inhibited by miR-21, and consequently inhibited proliferation and colony formation and triggered S-G2/M cell cycle arrest through the AKT pathway...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27862318/genome-wide-dna-methylation-analysis-identifies-megf10-as-a-novel-epigenetically-repressed-candidate-tumour-suppressor-gene-in-neuroblastoma
#9
Jessica Charlet, Ayumi Tomari, Anthony R Dallosso, Marianna Szemes, Martina Kaselova, Thomas J Curry, Bader Almutairi, Heather C Etchevers, Carmel McConville, Karim T A Malik, Keith W Brown
Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome-wide mutation analyses, many primary neuroblastomas do not contain recognisable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome-wide DNA methylation analysis...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27859625/loss-of-microrna-489-3p-promotes-osteosarcoma-metastasis-by-activating-pax3-met-pathway
#10
Qifei Liu, Guochun Yang, Yuying Qian
(OS) remains one deadly disease for many affected patients. MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-489-3p in osteosarcoma (OS) metastasis. MiR-489-3p expression was downregulated in OS cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-489-3p significantly suppressed OS cell invasion and metastasis both in vitro and in vivo...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27813185/new-orally-active-dna-minor-groove-binding-small-molecule-ct-1-acts-against-breast-cancer-by-targeting-tumor-dna-damage-leading-to-p53-dependent-apoptosis
#11
Karan Singh Saini, Hamidullah, Raghib Ashraf, Dhanaraju Mandalapu, Sharmistha Das, Mohd Quadir Siddiqui, Sonam Dwivedi, Jayanta Sarkar, Vishnu Lal Sharma, Rituraj Konwar
Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo...
November 4, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27805295/juxtaposed-genes-in-7q21-22-amplicon-contribute-for-two-major-gastric-cancer-sub-types-by-mutual-exclusive-expression
#12
Sembulingam Tamilzhalagan, Muthulakshmi Muthuswami, Kumaresan Ganesan
Genomic Copy Number Variations (CNV) and the associated gene signatures are useful for cancer prognosis, diagnosis, and targeted therapeutics. Earlier, 7q21-22 region was reported for frequent amplification in gastric cancer and potential candidate genes were identified. An analysis of the expression pattern of the 159 genes located in this amplicon revealed the consistent elevated expression of 21 genes in gastric tumors. These genes are closely arranged within the 20 Mb region, and they showed a bimodal expression pattern...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27805285/survivin-inhibitor-ym155-induces-mitochondrial-dysfunction-autophagy-dna-damage-and-apoptosis-in-bcl-xl-silenced-glioma-cell-lines
#13
Esther P Jane, Daniel R Premkumar, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
Because the anti-apoptotic protein Bcl-xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl-xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl-xL silenced cells with the survivin inhibitor, YM155...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27805284/susceptibility-loci-of-cnot6-in-the-general-mrna-degradation-pathway-and-lung-cancer-risk-a-re-analysis-of-eight-gwass
#14
Fei Zhou, Yanru Wang, Hongliang Liu, Neal Ready, Younghun Han, Rayjean J Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Irene Brüske, Angela Risch, Yuanqing Ye, Xifeng Wu, David C Christiani, Gary Goodman, Chu Chen, Christopher I Amos, Wei Qingyi
PURPOSE: mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities involved in mRNA degradation genes were found to be associated with cancer risk. Therefore, we systematically investigated the roles of genetic variants in the general mRNA degradation pathway in lung cancer risk. EXPERIMENTAL DESIGN: Meta-analyses were conducted using summary data from six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27805282/toll-like-receptor-3-stimulation-triggers-metabolic-reprogramming-in-pharyngeal-cancer-cell-line-through-myc-mapk-and-hif
#15
Tanja Matijevic Glavan, Ana Cipak Gasparovic, Benjamin Vérillaud, Pierre Busson, Jasminka Pavelic
Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27787930/stromal-contributions-to-the-carcinogenic-process
#16
Mark Spaw, Shrikant Anant, Sufi Mary Thomas
Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cellular components. Tumor-associated stromal cell types include the microbiome, immune cells including macrophages, dendritic and T-cells, cells associated with blood and lymphatic vessels including pericytes and endothelial cells, fibroblasts, neuronal cells, and adipocytes...
October 27, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27787915/resveratrol-inhibits-il-6-induced-ovarian-cancer-cell-migration-through-epigenetic-up-regulation-of-autophagy
#17
Alessandra Ferraresi, Suratchanee Phadngam, Federica Morani, Alessandra Galetto, Oscar Alabiso, Giovanna Chiorino, Ciro Isidoro
Interleukin-6 (IL-6), a pro-inflammatory cytokine released by cancer associated fibroblasts, has been linked to the invasive and metastatic behavior of ovarian cancer cells. Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol and IL-6 affect in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells...
October 27, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27770580/bcl2l10-inhibits-growth-and-metastasis-of-hepatocellular-carcinoma-both-in-vitro-and-in-vivo
#18
Yun Bai, Jia Wang, Jing Han, Xiao-Li Xie, Cheng-Guang Ji, Jie Yin, Lei Chen, Cun-Kai Wang, Xiao-Yu Jiang, Wei Qi, Hui-Qing Jiang
BACKGROUND AND AIMS: BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. METHODS: BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice...
October 22, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27769097/cancer-associated-fibroblasts-mediated-chemoresistance-by-a-foxo1-tgf%C3%AE-1-signaling-loop-in-esophageal-squamous-cell-carcinoma
#19
Hongfang Zhang, Conghua Xie, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yan Wang, Shixiu Wu
Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively...
October 21, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27753148/targeting-aberrant-expression-of-notch-1-in-aldh-cancer-stem-cells-in-breast-cancer
#20
Deeksha Pal, Venkatesh Kolluru, Balaji Chanderashekar, Becca V Baby, Mazzy Aman, Suman Suman, Suman Sirimulla, Mary Ann Sanders, Praveen Seshabhatter, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues...
October 18, 2016: Molecular Carcinogenesis
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