Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis
The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor ini...
Source: Molecular Oncology - February 29, 2016 Category: Cancer & Oncology Authors: Daniel R. Carter, Selina K. Sutton, Marina Pajic, Jayne Murray, Eric O. Sekyere, Jamie Fletcher, Anneleen Beckers, Katleen De Preter, Frank Speleman, Rani E. George, Michelle Haber, Murray D. Norris, Belamy B. Cheung, Glenn M. Marshall Source Type: research
Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over-expression in breast cancer
The 8p11-p12 amplicon occurs in approximately 15% of breast cancers in aggressive luminal B-type tumors. Previously, we identified WHSC1L1 as a driving oncogene from this region. Here, we demonstrate that over-expression of WHSC1L1 is linked to over-expression of ERα in SUM-44 breast cancer cells and in primary human breast cancers. Knock-down of WHSC1L1, particularly WHSC1L1-short, had a dramatic effect on ESR1 mRNA and ERα protein levels. SUM-44 cells do not require exogenous estrogen for growth in vitro; however, they are dependent on ERα expression, as ESR1 knock-down or exposure to the selective estrogen receptor d...
Source: Molecular Oncology - February 26, 2016 Category: Cancer & Oncology Authors: Jonathan Irish, Jamie N. Mills, Brittany Turner-Ivey, Robert Wilson, Stephen Guest, Alexandra Rutkovsky, Alan Dombkowski, Christiana Kappler, Gary Hardiman, Stephen P. Ethier Source Type: research
Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ER α in SUM-44 breast cancer cells and is associated with ERα over-expression in breast cancer
The 8p11-p12 amplicon occurs in approximately 15% of breast cancers in aggressive luminal B-type tumors. Previously, we identified WHSC1L1 as a driving oncogene from this region. Here, we demonstrate that over-expression of WHSC1L1 is linked to over-expression of ER α in SUM-44 breast cancer cells and in primary human breast cancers. Knock-down of WHSC1L1, particularly WHSC1L1-short, had a dramatic effect on ESR1 mRNA and ERα protein levels. SUM-44 cells do not require exogenous estrogen for growth in vitro; however, they are dependent on ERα expression, a s ESR1 knock-down or exposure to the selective estrogen recept...
Source: Molecular Oncology - February 25, 2016 Category: Cancer & Oncology Authors: Jonathan C. Irish, Jamie N. Mills, Brittany Turner-Ivey, Robert C. Wilson, Stephen T. Guest, Alexandria Rutkovsky, Alan Dombkowski, Christiana S. Kappler, Gary Hardiman, Stephen P. Ethier Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - February 25, 2016 Category: Cancer & Oncology Source Type: research
MicroRNA-548j Functions as a Metastasis Promoter in Human Breast Cancer by Targeting Tensin1
MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miRTM virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. (Source: Molecular Oncology)
Source: Molecular Oncology - February 22, 2016 Category: Cancer & Oncology Authors: Yun Zhan, Xiaoshuan Liang, Lin Li, Baona Wang, Fang Ding, Yi Li, Xiang Wang, Qimin Zhan, Zhihua Liu Source Type: research
MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1
MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miR ™ virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. (Source: Molecular Oncology)
Source: Molecular Oncology - February 21, 2016 Category: Cancer & Oncology Authors: Yun Zhan, Xiaoshuan Liang, Lin Li, Baona Wang, Fang Ding, Yi Li, Xiang Wang, Qimin Zhan, Zhihua Liu Source Type: research
Large-scale evaluation of in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels
Limitations of current diagnostic and prognostic tools for prostate cancer (PC) have led to over-diagnosis and over-treatment. Here, we investigate the biomarker potential of the SLC18A2 (VMAT2) gene for PC at three molecular levels. Thus, SLC18A2 promoter methylation was analyzed in 767 malignant and 78 benign radical prostatectomy (RP) samples using methylation-specific qPCR and Illumina 450K methylation microarray data. SLC18A2 transcript levels were assessed in 412 malignant and 45 benign RP samples using RNAseq data. (Source: Molecular Oncology)
Source: Molecular Oncology - February 12, 2016 Category: Cancer & Oncology Authors: Christa Haldrup, Anne-Sofie Lynnerup, Tine Maj Storebjerg, Søren Vang, Peter Wild, Tapio Visakorpi, Christian Arsov, Wolfgang A. Schulz, Johan Lindberg, Henrik Grönberg, Lars Egevad, Michael Borre, Torben Falck Ørntoft, Søren Høyer, Karina Dalsgaard Source Type: research
Large-scale evaluation of SLC18A2 in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels
Limitations of current diagnostic and prognostic tools for prostate cancer (PC) have led to over-diagnosis and over-treatment. Here, we investigate the biomarker potential of the SLC18A2 (VMAT2) gene for PC at three molecular levels. Thus, SLC18A2 promoter methylation was analyzed in 767 malignant and 78 benign radical prostatectomy (RP) samples using methylation-specific qPCR and Illumina 450K methylation microarray data. SLC18A2 transcript levels were assessed in 412 malignant and 45 benign RP samples using RNAseq data. (Source: Molecular Oncology)
Source: Molecular Oncology - February 12, 2016 Category: Cancer & Oncology Authors: Christa Haldrup, Anne-Sofie Lynnerup, Tine Maj Storebjerg, Søren Vang, Peter Wild, Tapio Visakorpi, Christian Arsov, Wolfgang A. Schulz, Johan Lindberg, Henrik Grönberg, Lars Egevad, Michael Borre, Torben Falck Ørntoft, Søren Høyer, Karina Dalsgaard Source Type: research
Clinical and biological significance of circulating tumor cells in cancer
During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatme...
Source: Molecular Oncology - February 9, 2016 Category: Cancer & Oncology Authors: Takaaki Masuda, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori Tags: Review Source Type: research
Gene expression profiling and DNA methylation analyses of CTCs
A variety of molecular assays have been developed for CTCs detection and molecular characterization. Molecular assays are based on the nucleic acid analysis in CTCs and are based on total RNA isolation and subsequent mRNA quantification of specific genes, or isolation of genomic DNA that can be for DNA methylation studies and mutation analysis. This review is mainly focused on gene expression and methylation studies in CTCs in various types of cancer. (Source: Molecular Oncology)
Source: Molecular Oncology - February 5, 2016 Category: Cancer & Oncology Authors: Evi S. Lianidou Source Type: research
Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs
Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitan...
Source: Molecular Oncology - February 3, 2016 Category: Cancer & Oncology Authors: Xinlai Cheng, Jee Young Kim, Shahrouz Ghafoory, Tijen Duvaci, Roya Rafiee, Jannick Theobald, Hamed Alborzinia, Pavlo Holenya, Johannes Fredebohm, Karl-Heinz Merz, Arianeb Mehrabi, Mohammadreza Hafezi, Arash Saffari, Gerhard Eisenbrand, Jörg D. Hoheisel, Source Type: research
Liquid biopsy: Potential and challenges
Current molecular diagnostics in cancer patients is based on needle biopsies, which, however, face serious limitations which can lead to false decisions. Individual tumors consist of diverse subpopulations, and the small amount of tissue obtained by needle biopsies may not represent the most aggressive subclones. Moreover, some tumor entities such as lung cancer are located at remote sites and a needle biopsy can be very difficult and at high risk. Finally, the mere analysis of the resected primary tumor alone (current standard practise in oncology) may provide misleading information with regard to the characteristics of m...
Source: Molecular Oncology - February 1, 2016 Category: Cancer & Oncology Authors: Klaus Pantel, Catherine Alix-Panabieres Source Type: research
