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https://www.readbyqxmd.com/read/28109176/oncogenic-roles-of-smarcb1-ini1-and-its-deficient-tumors
#1
Kenichi Kohashi, Yoshinao Oda
SMARCB1/INI1 is one of the core subunit proteins of the ATP-dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16-RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non-tumorous tissue showed SMARCB1/INI1 protein expression...
January 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28109115/-research-progress-of-mirnas-targeting-gsk-3%C3%AE-in-regulation-of-hepatocellular-carcinoma-invasion-and-metastasis
#2
Song-Qi He, Bin Wen, Guan-Xin Chen, Hai-Tao Sun, Jia-Ling Sun, Xue-Mei Yang
Invasion and metastasis are key factors contributing to the high mortality rate of patients with hepatocellular carcinoma (HCC) involving a complex mechanism. In the invasion and metastasis of HCC, miRNAs can serve as either oncogenes or tumor suppressor genes to regulate the differentiation and proliferation of tumor cells being and play important roles in tumorigenesis, angiogenesis, invasion and metastasis. This review summarizes the recent progress in research of the molecular mechanisms by which miRNAs targeting GSK-3β regulate HCC invasion and metastasis and examines the roles of miRNAs in hepatocellular carcinoma cell proliferation, apoptosis, invasion, metastasis, and GSK-3β regulation...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28108766/immunosuppressive-myeloid-derived-suppressor-cells-are-increased-in-splenocytes-from-cancer-patients
#3
Kimberly R Jordan, Puja Kapoor, Eric Spongberg, Richard P Tobin, Dexiang Gao, Virginia F Borges, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice...
January 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#4
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T helper (Th1) cells and CD8(+) T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity towards CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#5
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
: Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
November 15, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108622/a-genome-wide-loss-of-function-screen-identifies-slc26a2-as-a-novel-mediator-of-trail-resistance
#6
Lina Dimberg, Christina G Towers, Kian Behbakht, Taylor Hotz, Jihye Kim, Susan P Fosmire, Christopher C Porter, Aik-Choon Tan, Andrew Thorburn, Heide L Ford
: TNF-related apoptosis inducing ligand (TRAIL) is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108288/klf4-expression-enhances-the-efficacy-of-chemotherapy-drugs-in-ovarian-cancer-cells
#7
Baojin Wang, Airong Shen, Xuan Ouyang, Guannan Zhao, Ziyun Du, Wenying Huo, Tao Zhang, Yinan Wang, Chuanhe Yang, Peixin Dong, Hidemichi Watari, Lawrence M Pfeffer, Junming Yue
KLF4 is a transcriptional factor that can function either as a tumor suppressor or oncogene in cancer based on its cellular context. We recently demonstrated that KLF4 was a tumor suppressor in ovarian cancer cells by inhibiting the epithelial to mesenchymal transition. Here we report that KLF4 expression was downregulated in ovarian cancer tissue compared to normal ovarian tissue, and low KLF4 expression correlated with high risk ovarian carcinoma and poor patient survival. Enforced KLF4 expression by lentiviral transduction sensitized ovarian cancer cells to the effects of the chemotherapy drugs, paclitaxel and cisplatin...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28108217/cdk3-is-a-major-target-of-mir-150-in-cell-proliferation-and-anti-cancer-effect
#8
Liang Wang, Yongyong Xi, Chengcao Sun, Feng Zhang, Heng Jiang, Qiqiang He, Dejia Li
MiR-150, a member of small non-coding RNAs, has been proven to dysregulate in different types of tumor and bear on carcinogenesis and cancer prognosis by regulating the expression of a series of gene including utrophin. Given that utrophin can compensate for dystrophin's absence and be regarded as a promising therapeutic target for Duchenne Muscular Dystrophy (DMD), we further detected the deep role of miR-150 in dystrophic muscle. Using a range of bioinformatic, molecular and cell biology techniques, we declared that miR-150 directly targets cyclin-dependent kinase 3 (CDK3) and leads to the regulation of CDK3 gene expression in both muscle-derived and non-muscle cells...
January 17, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28107872/mir-21-targets-and-inhibits-tumor-suppressor-gene-pten-to-promote-prostate-cancer-cell-proliferation-and-invasion-an-experimental-study
#9
Yu Yang, Jia-Xiang Guo, Zhi-Qiang Shao
OBJECTIVE: To study whether miR-21 targets and inhibits tumor suppressor gene PTEN can promote prostate cancer cell proliferation and invasion. METHODS: Prostate cancer cell lines PC-3 were cultured and divided into negative control group (NC group), miR-21 group, pcDNA3.1 group, miR-21+pcDNA3.1 group and miR-21+PTEN group that were transfected with different miR and plasmid, respectively. After 12 h and 24 h of transfection, the cell viability and invasive cell number were determined; after 24 h of transfection, Bcl-2, Survivin, MMP2, MMP9, PTEN, PI3K, and AKT expression in cells were determined...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107544/cutaneous-hpv8-and-mmupv1-e6-proteins-target-the-notch-and-tgf-%C3%AE-tumor-suppressors-to-inhibit-differentiation-and-sustain-keratinocyte-proliferation
#10
Jordan M Meyers, Aayushi Uberoi, Miranda Grace, Paul F Lambert, Karl Munger
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107519/cudraflavone-c-induces-tumor-specific-apoptosis-in-colorectal-cancer-cells-through-inhibition-of-the-phosphoinositide-3-kinase-pi3k-akt-pathway
#11
Hsien-Chuen Soo, Felicia Fei-Lei Chung, Kuan-Hon Lim, Veronica Alicia Yap, Tracey D Bradshaw, Ling-Wei Hii, Si-Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Chee-Onn Leong, Chun-Wai Mai
Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#12
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28107196/wilms-tumor-gene-1-silencing-inhibits-proliferation-of-human-osteosarcoma-mg-63-cell-line-by-cell-cycle-arrest-and-apoptosis-activation
#13
Adriana Carol Eleonora Graziano, Venera Cardile, Rosanna Avola, Nunzio Vicario, Carmela Parenti, Lucia Salvatorelli, Gaetano Magro, Rosalba Parenti
Wilms' tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. A high WT1 expression level was described in various types of human bone and soft-tissue sarcomas, including osteosarcoma (OS), but its function in carcinogenesis is not yet well understood. This study investigated WT1 both in human OS tissues and in human OS MG-63 cell line in which WT1 gene is up-regulated. The results demonstrated that WT1 is expressed in 50% of human OS cases...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107193/microrna-744-promotes-prostate-cancer-progression-through-aberrantly-activating-wnt-%C3%AE-catenin-signaling
#14
Han Guan, Chunhui Liu, Fang Fang, Yeqing Huang, Tao Tao, Zhixin Ling, Zonghao You, Xu Han, Shuqiu Chen, Bin Xu, Ming Chen
Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107179/nuclear-prmt5-cyclin-d1-and-il-6-are-associated-with-poor-outcome-in-oropharyngeal-squamous-cell-carcinoma-patients-and-is-inversely-associated-with-p16-status
#15
Bhavna Kumar, Arti Yadav, Nicole V Brown, Songzhu Zhao, Michael J Cipolla, Paul E Wakely, Alessandra C Schmitt, Robert A Baiocchi, Theodoros N Teknos, Matthew Old, Pawan Kumar
Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106991/discovery-of-a-phosphoinositide-3-kinase-pi3k-b-d-inhibitor-for-the-treatment-of-phosphatase-and-tensin-homolog-pten-deficient-tumors-building-pi3kb-potency-in-a-pi3kd-selective-template-by-targeting-non-conserved-asp856
#16
Stéphane Perreault, Jayaraman Chandrasekhar, Zhi-Hua Cui, Jerry B Evarts, Jia Hao, Joshua A Kaplan, Adam Kashishian, Kathleen S Keegan, Thomas Kenney, David J Koditek, Latesh Lad, Eve-Irene Lepist, Mary E McGrath, Leena Patel, Bart Phillips, Joseph Therrien, Jennifer Treiberg, Anella Yahiaoui, Gary Phillips
Phosphoinositide 3-kinase (PI3K) beta signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kbeta/delta inhibitors in which PI3Kbeta potency was built in a PI3Kdelta-selective template. This work led to the discovery of a highly selective PI3Kbeta/delta inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28106852/tumor-derived-tissue-factor-aberrantly-activates-complement-and-facilitates-lung-tumor-progression-via-recruitment-of-myeloid-derived-suppressor-cells
#17
Xiao Han, Haoran Zha, Fei Yang, Bo Guo, Bo Zhu
The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106301/uxt-is-a-lox-pp-interacting-protein-that-modulates-estrogen-receptor-alpha-activity-in-breast-cancer-cells
#18
Nuria Sánchez-Morgan, Kathrin H Kirsch, Philip C Trackman, Gail E Sonenshein
The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously eXpressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106296/pten-plays-dual-roles-as-a-tumor-suppressor-in-osteosarcoma-cells
#19
Yongming Xi, Yan Chen
Osteosarcoma (OS) is the most common primary bone cancer, which occurs primarily in children and adolescents. Functional loss of the tumor suppressor PTEN has been demonstrated in bone malignancies including OS. We have recently reported that Pten expression inversely correlates with OS aggressiveness in mouse models. However, the mechanism whereby PTEN exerts its anti-tumor effect remains unknown. In this study, we first examined the expression of PTEN in human OS cell lines including U2OS, MG63 and Saos-2, and found that PTEN expression is reduced as compared to normal human osteoblasts...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105922/differential-expression-of-alternatively-spliced-transcripts-related-to-energy-metabolism-in-colorectal-cancer
#20
Anastasiya Vladimirovna Snezhkina, George Sergeevich Krasnov, Andrew Rostislavovich Zaretsky, Alex Zhavoronkov, Kirill Mikhailovich Nyushko, Alexey Alexandrovich Moskalev, Irina Yurievna Karpova, Anastasiya Isaevna Afremova, Anastasiya Valerievna Lipatova, Dmitriy Vladimitovich Kochetkov, Maria Sergeena Fedorova, Nadezhda Nikolaevna Volchenko, Asiya Fayazovna Sadritdinova, Nataliya Vladimirovna Melnikova, Dmitry Vladimirovich Sidorov, Anatoly Yurievich Popov, Dmitry Valerievich Kalinin, Andrey Dmitrievich Kaprin, Boris Yakovlevich Alekseev, Alexey Alexandrovich Dmitriev, Anna Viktorovna Kudryavtseva
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC...
December 28, 2016: BMC Genomics
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