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Suppressor cells

Raffaella Sordella, Nitin H Shirole, Debjani Pal, Edward R Kastenhuber, Serif Senturk, Joseph Boroda, Paola Pisterzi, Madison Miller, Gustavo Munoz, Marko Anderluh, Marc Ladanyi, Scott W Lowe
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD)...
October 19, 2016: ELife
Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Yuping Wang, Qin Dong, Yang Gu, Lynn J Groome
PROBLEM: To determine whether miR-203 mediates endothelial inflammatory response in preeclampsia. METHOD OF STUDY: Maternal vessel miR-203 expression was assessed by in situ hybridization. Suppressor of cytokine signaling-3 (SOCS-3) and ICAM expression was determined by immunostaining. Subcutaneous fat tissue sections from normal and preeclamptic pregnant women were used. miR-203-induced inflammatory response was evaluated by the measurements of IL-6, IL-8, ICAM, and VCAM expression and production and neutrophil adhesion in the endothelial cells (EC) transfected with miR-203 precursor, pre-miR-203...
October 18, 2016: American Journal of Reproductive Immunology: AJRI
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Xin Long, Jian Wang, Jian-Ping Zhao, Hui-Fang Liang, Peng Zhu, Qi Cheng, Qian Chen, Yan-Hui Wu, Zhan-Guo Zhang, Bi-Xiang Zhang, Xiao-Ping Chen
The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group)...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Ching-Hao Li, Chen-Wei Liu, Chi-Hao Tsai, Yi-Jen Peng, Yu-Hsuan Yang, Po-Lin Liao, Chen-Chen Lee, Yu-Wen Cheng, Jaw-Jou Kang
Aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been studied extensively in carcinogenesis through the genomic pathway. In recent years, AHR has also been reported to exert positive or negative effects on epithelial-mesenchymal transition (EMT), the crucial step in tumor malignant progression. However, the detailed mechanism remains controversial. Analysis of AHR-expression levels in non-small cell lung cancer cell lines and lung cancer tissues revealed an inverse correlation between AHR protein levels and tumor cell invasion and metastasis...
October 17, 2016: Archives of Toxicology
Kallirroi Voudouri, Dragana Nikitovic, Aikaterini Berdiaki, John Tsiaoussis, Dimitris Kletsas, Nikos K Karamanos, George N Tzanakakis
In this data article, the potential role of p53 tumor suppressor gene (p53) on the attachment ability of MCF-7 breast cancer cells was investigated. In our main article, "IGF-I/ EGF and E2 signaling crosstalk through IGF-IR conduit point affect breast cancer cell adhesion" (K. Voudouri, D. Nikitovic, A. Berdiaki, D. Kletsas, N.K. Karamanos, G.N. Tzanakakis, 2016) [1], we describe the key role of IGF-IR in breast cancer cell adhesion onto fibronectin (FN). p53 tumor suppressor gene is a principal regulator of cancer cell proliferation...
December 2016: Data in Brief
Nurbek Mambetsariev, Wai W Lin, Alicia M Wallis, Laura L Stunz, Gail A Bishop
The adaptor protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival. B cell-specific TRAF3 deficiency results in enhanced viability and is associated with development of lymphoma and multiple myeloma. We show that TRAF3 deficiency led to induction of two proteins important for glucose metabolism, Glut1 and Hexokinase 2 (HXK2). This was associated with increased glucose uptake. In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylation were increased in B cells without changes in mitochondrial mass or reactive oxygen species...
October 18, 2016: Scientific Reports
Irsan E Kooi, Saskia E van Mil, David MacPherson, Berber M Mol, Annette C Moll, Hanne Meijers-Heijboer, Gertjan J L Kaspers, Jacqueline Cloos, Hein Te Riele, Josephine C Dorsman
Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130. In Rb(-/-) p107(-/-) retinoblastomas, somatic copy number alterations (SCNAs) like Mdm2 amplification or Cdkn2a deletion targeting the p53-pathway occur, which is uncommon for human retinoblastoma. In our study, we determined SCNAs in retinoblastomas developing in Rb(-/-) p130(-/-) mice and compared this to murine Rb(-/-) p107(-/-) tumors and human tumors...
October 17, 2016: Genes, Chromosomes & Cancer
Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a non-random distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells...
October 17, 2016: Genes, Chromosomes & Cancer
Kriti Sethi, Saravanan Palani, Juan C G Cortés, Mamiko Sato, Mayalagu Sevugan, Mariona Ramos, Shruthi Vijaykumar, Masako Osumi, Naweed I Naqvi, Juan Carlos Ribas, Mohan Balasubramanian
Cytokinesis in many organisms requires a plasma membrane anchored actomyosin ring, whose contraction facilitates cell division. In yeast and fungi, actomyosin ring constriction is also coordinated with division septum assembly. How the actomyosin ring interacts with the plasma membrane and the plasma membrane-localized septum synthesizing machinery remains poorly understood. In Schizosaccharomyces pombe, an attractive model organism to study cytokinesis, the β-1,3-glucan synthase Cps1p / Bgs1p, an integral membrane protein, localizes to the plasma membrane overlying the actomyosin ring and is required for primary septum synthesis...
October 2016: PLoS Genetics
Jia-Jie Hao, De-Chen Lin, Huy Q Dinh, Anand Mayakonda, Yan-Yi Jiang, Chen Chang, Ye Jiang, Chen-Chen Lu, Zhi-Zhou Shi, Xin Xu, Yu Zhang, Yan Cai, Jin-Wu Wang, Qi-Min Zhan, Wen-Qiang Wei, Benjamin P Berman, Ming-Rong Wang, H Phillip Koeffler
Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others...
October 17, 2016: Nature Genetics
Lin Xu, Zhu Wang, Shan-Yang He, Su-Fen Zhang, Hong-Jiao Luo, Kai Zhou, Xiao-Fei Li, Shao-Peng Qiu, Kai-Yuan Cao
Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear...
October 14, 2016: Oncology Reports
Yanke Chen, Xiaofei Wang, Jiwen Cheng, Zhen Wang, Ting Jiang, Ni Hou, Na Liu, Tusheng Song, Chen Huang
Growing evidence indicates that some abnormally expressed microRNAs (miRNAs) influence tumorigenesis and progression. Previous studies reported that miR-20a is among the frequently altered miRNAs in human hepatocellular carcinoma (HCC), but its expression pattern and role in HCC remain controversial. In the present study, we demonstrated that miR-20a-5p exhibited aberrant expression in HCC tissues compared with paired non-tumor tissues: 52% of the tumor samples showed a greater increase. Overexpression of miR-20a contributed to HCC cell proliferation and migration in vitro, and treatment with anti-miR20a-5p caused the opposite effects...
October 4, 2016: Oncology Reports
Hongyan Zhou, Jie Li, Zhanqiang Zhang, Runyi Ye, Nan Shao, Tuckyun Cheang, Shenming Wang
Evidence suggests that RING1 and YY1 binding protein (RYBP) functions as a tumor suppressor. However, its role in breast cancer remains unclear. In the present study, the expression of RYBP was assessed in breast cancer patients and cell lines. Disease-free survival durations of breast cancer patients with high RYBP expression were determined based on the ATCG dataset. The effects of RYBP overexpression on cell growth, migration and invasive potency were also assessed. Nude mouse xenograft and lung metastasis models were also used to confirm the role of RYBP...
October 5, 2016: International Journal of Oncology
Shanmei Du, Helou Li, Xiaochun Sun, Dongsheng Li, Yong Yang, Zehua Tao, Qian Li, Kui Liu
MicroRNA (miRNA) is a type of endogenous non‑coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines...
October 11, 2016: Oncology Reports
Jingwei Jiang, Qingmin Gao, Tian Wang, Hao Lin, Qiong Zhan, Zhaohui Chu, Ruofan Huang, Xinli Zhou, Xiaohua Liang, Weijian Guo
Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G‑MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G‑MDSCs were determined and the differential expression of microRNAs between G‑MDSCs from tumor‑bearing mice and tumor‑free mice was examined. The number of G‑MDSCs in spleens of Lewis lung carcinoma (LLC)‑bearing mice was ~6‑fold higher than in spleens of normal mice (13...
October 13, 2016: Molecular Medicine Reports
Wei Zhang, Jianzhou Liu, Jianxin Qiu, Xiaoliang Fu, Qisheng Tang, Fan Yang, Zhiguang Zhao, He Wang
MicroRNAs (miRNAs) have emerged as important regulators in cancer that are implicated in regulation of various cellular processes. miR-382 has been proposed as a tumor suppressor by several recent studies. However, the function of miR-382 in prostate cancer remains unknown. In this study, we aimed to investigate the potential function of miR-382 in prostate cancer. We found that miR-382 was significantly decreased in prostate cancer specimens and cancer cell lines. The overexpression of miR-382 in prostate cancer cells markedly inhibited cell proliferation, migration, and invasion...
October 3, 2016: Oncology Reports
Yu Zhou, Yang Liu, Chao Hu, Yugang Jiang
MicroRNAs (miRNAs or miRs), a class of non-coding RNAs 18-25 nucleotides in length, act as key regulators in the development and malignant progression of various human cancers by modulating the expression of their target genes. Recently, miR‑16 has been demonstrated to be play a role in glioma. However, the regulatory mechanisms of miR‑16 in glioma growth and metastasis remain largely unclear. In the present study, qRT-PCR revealed that miR‑16 was significantly downregulated in 23 glioma tissue specimens compared to 7 normal brain tissue specimens...
October 17, 2016: International Journal of Molecular Medicine
Xueyan Zhang, Katsuyoshi Takata, Wei Cui, Tomoko Miyata-Takata, Yasuharu Sato, Mai Noujima-Harada, Tadashi Yoshino
Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH‑γ subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH‑γ subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH‑γ gene subfamily member, in B‑cell lymphoma 2 (BCL2)‑positive and ‑negative FL, and evaluated its association with tumor cell proliferation in an FL‑derived cell line...
October 5, 2016: Molecular Medicine Reports
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