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Molecular Cancer Research: MCR

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https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#1
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27899423/myc-mediates-mrna-cap-methylation-of-canonical-wnt-beta-catenin-signaling-transcripts-by-recruiting-cdk7-and-rna-methyltransferase
#2
Valeriya Posternak, Matthew H Ung, Chao Cheng, Michael D Cole
: MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/beta-catenin signaling...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27899422/high-risk-hpv-biomarkers-and-outcome-in-matched-cohorts-of-head-and-neck-cancer-patients-positive-and-negative-for-hiv
#3
Heather M Walline, Thomas E Carey, Christine M Goudsmit, Emily L Bellile, Gypsyamber D'souza, Lisa A Peterson, Jonathan B McHugh, Sara I Pai, J Jack Lee, Dong M Shin, Robert L Ferris
: In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR and In Situ Hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27864334/deubiquitinase-otud6b-isoforms-are-important-regulators-of-growth-and-proliferation
#4
Anna Sobol, Caroline Askonas, Sara Alani, Megan J Weber, Vijayalakshmi Ananthanarayanan, Clodia Osipo, Maurizio Bocchetta
: Deubiquitinases (DUBs) are increasingly linked to the regulation of fundamental processes in normal and cancer cells, including DNA replication and repair, programmed cell death, and oncogenes and tumor suppressors signaling. Here evidence is presented that the deubiquitinase OTUD6B regulates protein synthesis in non-small cell lung cancer (NSCLC) cells, operating downstream from mTORC1. OTUD6B associates with the protein synthesis initiation complex and modifies components of the 48S preinitiation complex...
November 18, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27864333/oncogenic-kras-targets-muc16-ca125-in-pancreatic-ductal-adenocarcinoma
#5
Xianjun Yu, Chen Liang, Yi Qin, Bo Zhang, Shunrong Ji, Si Shi, Wenyan Xu, Jiang Liu, Jin-Feng Xiang, Dingkong Liang, Qiangsheng Hu, Quanxing Ni, Jin Xu
: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with the 5-year survival rate less than 6%. Previous results indicated that serum levels of CA125 (encoded by MUC16) could be used to predict which groups of pancreatic cancer patients may benefit from surgery. However, the underlying mechanism remains elusive. Herein, using the Cancer Genome Atlas (TCGA) and clinicopathological data obtained from our center, we demonstrate that high CA125 serum levels and expression levels of MUC16 are predictive of poor prognosis...
November 18, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27856957/nuclear-localized-lsr-a-novel-regulator-of-breast-cancer-behavior-and-tumorigenesis
#6
Denise K Reaves, Katherine A Hoadley, Katerina Fagan-Solis, Dereje D Jima, Michael Bereman, Lynnelle Thorpe, Jyla Hicks, David McDonald, Melissa A Troester, Charles M Perou, Jodie M Fleming
: Lipolysis Stimulated Lipoprotein Receptor (LSR) has been found in the plasma membrane and is believed to function in lipoprotein endocytosis and tight junctions. Given the impact of cellular metabolism and junction signaling pathways on tumor phenotypes and patient outcome, it is important to understand how LSR cellular localization mediates its functions. We conducted localization studies, evaluated DNA binding, and examined the effects of nuclear LSR in cells, xenografts, and clinical specimens...
November 17, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27856956/the-efflux-transporter-abcg2-maintains-prostate-stem-cells
#7
Neha G Sabnis, Austin Miller, Mark A Titus, Wendy J Huss
: Prostate Stem Cells (PSCs) are characterized by their intrinsic resistance to Androgen Deprivation Therapy (ADT), possibly due to the lack of Androgen Receptor (AR) expression. PSCs resistance to ADT and PSC expansion in Castration Recurrent Prostate Cancer (CRPC) has sparked great interest in using differentiation therapy as an adjuvant to ADT. Understanding the mechanisms, by which PSCs maintain their undifferentiated phenotype, thus has important implications in differentiation therapy...
November 17, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27852646/metabolic-reprogramming-by-folate-restriction-leads-to-a-less-aggressive-cancer-phenotype
#8
Zahra Ashkavand, Ciara O'Flanagan, Mirko Hennig, Xiuxia Du, Stephen D Hursting, Sergey A Krupenko
: Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration and survival in many cell types. Here the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: non-invasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wntliver) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors...
November 16, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27807188/autophagy-induction-results-in-enhanced-anoikis-resistance-in-models-of-peritoneal-disease
#9
James L Chen, Jason David, Douglas Cook-Spaeth, Sydney Casey, David Cohen, Karuppaiyah Selvendiran, Tanios Bekaii-Saab, John Hays
: Peritoneal carcinomatosis and peritoneal sarcomatosis (PC/PS) is a potential complication of nearly all solid tumors and results in profoundly increased morbidity and mortality. Despite the ubiquity of PC/PS, there are no clinically relevant targeted therapies for either its treatment or prevention. To identify potential therapies, we developed in vitro models of PC/PS using tumor cell lines and patient-derived spheroids (PDS) that recapitulate anoikis resistance and spheroid proliferation across multiple cancer types...
November 2, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27760843/exosomal-annexin-a2-promotes-angiogenesis-and-breast-cancer-metastasis
#10
Sayantan Maji, Pankaj Chaudhary, Irina Akopova, Phung M Nguyen, Richard J Hare, Ignacy Gryczynski, Jamboor K Vishwanatha
: Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin A2 as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal-AnnexinA2 (exo-AnxA2) are still lacking. In this study, mechanistic insight was sought regarding exo-AnxA2 and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-AnxA2 in angiogenesis...
October 19, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27758876/exosomes-promote-ovarian-cancer-cell-invasion-through-transfer-of-cd44-to-peritoneal-mesothelial-cells
#11
Koji Nakamura, Kenjiro Sawada, Yasuto Kinose, Akihiko Yoshimura, Aska Toda, Erika Nakatsuka, Kae Hashimoto, Seiji Mabuchi, Ken-Ichirou Morishige, Hirohisa Kurachi, Ernst Lengyel, Tadashi Kimura
: Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMCs) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications are exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs...
October 6, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27707887/overcoming-egfr-bypass-signal-induced-acquired-resistance-to-alk-tyrosine-kinase-inhibitors-in-alk-translocated-lung-cancer
#12
Masayoshi Miyawaki, Hiroyuki Yasuda, Tetsuo Tani, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Yuichiro Hayashi, Tomoko Betsuyaku, Kenzo Soejima
: Activation of the epidermal growth factor receptor (EGFR) pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLCs) harboring the ALK gene rearrangement. However, the precise mechanism underlying acquired resistance to ceritinib is not well defined. This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway-induced acquired resistance to ALK-TKIs...
October 5, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27707886/exploitation-of-castration-resistant-prostate-cancer-transcription-factor-dependencies-by-the-novel-bet-inhibitor-abbv-075
#13
Emily J Faivre, Denise Wilcox, Xiaoyu Lin, Paul Hessler, Maricel Torrent, Wei He, Tamar Uziel, Daniel H Albert, Keith McDaniel, Warren Kati, Yu Shen
: Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and hematologic malignancies. The function of BET family member BRD4 at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here the hypothesis was tested that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075...
October 5, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27698077/src-family-kinases-are-regulated-in-multiple-myeloma-cells-by-phosphatase-of-regenerating-liver-3
#14
Pegah Abdollahi, Esten Nymoen Vandsemb, Magnus Aassved Hjort, Kristine Misund, Toril Holien, Anne-Marit Sponaas, Torstein B Ro, Tobias S Slordahl, Magne Borset
: Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual specificity phosphatase that is up-regulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several anti-apoptotic cytokines, including interleukin-6 (IL6), in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6...
October 3, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27678171/senescent-carcinoma-associated-fibroblasts-upregulate-il8-to-enhance-pro-metastatic-phenotypes
#15
Tao Wang, Faiyaz Notta, Roya Navab, Joella Joseph, Emin Ibrahimov, Jing Xu, Chang-Qi Zhu, Ayelet Borgida, Steven Gallinger, Ming-Sound Tsao
: Carcinoma associated fibroblasts (CAFs) represent a significant component of pancreatic cancer stroma and are biologically implicated in tumour progression. However, evidence of both cancer promoting and restraining properties amongst CAFs suggests the possibility of multiple phenotypic subtypes. Here, it is demonstrated that senescent CAFs promote pancreatic cancer invasion and metastasis compared to non-senescent control CAFs using in vitro transwell invasion models and in vivo xenograft mouse models...
September 27, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27671337/interplay-between-cytoplasmic-and-nuclear-androgen-receptor-splice-variants-mediate-castration-resistance
#16
Yang Zhan, Guanyi Zhang, Xiaojie Wang, Yangfeng Qi, Dongyi Li, Shanshan Bai, Tianfang Ma, Erik K Flemington, Haitao Zhang, Oliver Sartor, Peng Lee, Yan Dong
: Androgen receptor splice variants (AR-Vs) are implicated in resistance of prostate cancer to androgen-directed therapies. When expressed alone in cells, some AR-Vs (e.g., AR-V7) localize primarily to the nucleus, whereas others (e.g., AR-V1, AR-V4, and AR-V6) localize mainly to the cytoplasm. Significantly, the latter are often co-expressed with the nucleus-predominant AR-Vs and the full-length AR (AR-FL). An important question to be addressed is whether the cytoplasmic-localized AR-Vs play a role in castration-resistant prostate cancer (CRPC) through interaction with the nucleus-predominant AR-Vs and AR-FL...
September 26, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27671335/ecm-composition-and-rheology-regulate-growth-motility-and-response-to-photodynamic-therapy-in-3d-models-of-pancreatic-ductal-adenocarcinoma
#17
Gwendolyn M Cramer, Dustin P Jones, Hamid El Hamidi, Jonathan P Celli
: Pancreatic ductal adenocarcinoma (PDAC) is characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich PDAC stroma has been implicated as a barrier to drug penetration, though stromal depletion strategies have had mixed clinical success. It remains less clear how interactions with ECM, acting as a biophysical regulator of phenotype, not only a barrier to drug perfusion, regulate susceptibilities and resistance to specific therapies...
September 26, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27671334/axl-inhibition-suppresses-the-dna-damage-response-and-sensitizes-cells-to-parp-inhibition-in-multiple-cancers
#18
Kavitha Balaji, Smruthi Vijayaraghavan, Lixia Diao, Pan Tong, Youhong Fan, Jason Pw Carey, Tuyen N Bui, Steven Warner, John V Heymach, Kelly K Hunt, Jing Wang, Lauren Averett Byers, Khandan Keyomarsi
: Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non-small cell lung cancers (NSCLCs) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBCs) and head and neck squamous cell carcinomas (HNSCCs) and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to chemotherapy, radiation, and targeted therapy...
September 26, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27913704/highlights-of-this-issue
#19
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December 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27671336/integrated-genetic-epigenetic-and-transcriptional-profiling-identifies-molecular-pathways-in-the-development-of-laterally-spreading-tumors
#20
Luke B Hesson, Benedict Ng, Peter Zarzour, Sameer Srivastava, Chau-To Kwok, Deborah Packham, Andrea C Nunez, Dominik Beck, Regina Ryan, Ashraf Dower, Caroline E Ford, John E Pimanda, Mathew A Sloane, Nicholas J Hawkins, Michael J Bourke, Jason W H Wong, Robyn L Ward
: Laterally spreading tumors (LST) are colorectal adenomas that develop into extremely large lesions with predominantly slow progression to cancer, depending on lesion subtype. Comparing and contrasting the molecular profiles of LSTs and colorectal cancers offers an opportunity to delineate key molecular alterations that drive malignant transformation in the colorectum. In a discovery cohort of 11 LSTs and paired normal mucosa, we performed a comprehensive and unbiased screen of the genome, epigenome, and transcriptome followed by bioinformatics integration of these data and validation in an additional 84 large, benign colorectal lesions...
December 2016: Molecular Cancer Research: MCR
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