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Tinglei Huang, Meiling Wang, Bo Huang, Augustus Chang, Feng Liu, Yanjie Zhang, Bin Jiang
As an evolutionarily conserved serine/threonine kinase of the phosphoinositide 3-kinase (PI3K) related kinase family, the mechanistic/mammalian target of rapamycin (mTOR) plays vital roles in the PI3K/AKT/mTOR pathway, participating in different cellular processes including cell survival, metabolism and proliferation. Aberrant activity of this signaling pathway may lead to oncogenesis. Over the last two decades, great progress has been made in the understanding of mTOR activation and how its response is counteracted for maintaining tissue homeostasis...
March 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
Cunzhen Shi, Xiangqun Li, Xiaogan Wang, Ning Ding, Lingyan Ping, Yunfei Shi, Lan Mi, Yumei Lai, Yuqin Song, Jun Zhu
BACKGROUND: Mantle cell lymphoma (MCL) is an incurable B cell-derived malignant tumor with a median overall survival of 4-5 years. Mer tyrosine kinase (MerTK) has been reported to be aberrantly expressed in leukemia, melanoma, and gastric cancer, and plays a pivotal role in the process of oncogenesis. This study assessed the role of MerTK in MCL for the first time. METHODS: Immunohistochemistry and western blot were performed to figure out expression of MerTK in MCL...
March 20, 2018: Journal of Hematology & Oncology
Stephen Capone, Kwasi M Connor, Anthony Colombo, Xin Li, Tim J Triche, Giridharan Ramsingh
Genomic transposable elements (TEs) constitute majority of the genome. Expression of TEs is known to activate the double-stranded RNA recognition pathway ("viral mimicry") leading to the activation of interferon-stimulated genes, inflammation and immune mediated cell death. We recently showed that the expression of TEs is suppressed along with immune pathways in leukemic stem cells (LSC) in acute myeloid leukemia, suggesting a potential mechanism for immune escape of LSC. This indicated that during oncogenesis, where there is escape from senescence, expression of TEs is suppressed...
March 13, 2018: Experimental Hematology
Renata Gruszka, Magdalena Zakrzewska
The fundamental function of ribonucleic acids is to transfer genetic information from DNA to protein during translation process, however, this is not the only way connecting active RNA sequences with essential biological processes. Up until now, many RNA subclasses of different size, structure, and biological function were identified. Among them, there are non-coding single-stranded microRNAs (miRNAs). This subclass comprises RNAs of 19-25 nucleotides in length that modulate the activity of well-defined coding RNAs and play a crucial role in many physiological and pathological processes...
March 16, 2018: International Journal of Molecular Sciences
Muthu K Shanmugam, Frank Arfuso, Surendar Arumugam, Arunachalam Chinnathambi, Bian Jinsong, Sudha Warrier, Ling Zhi Wang, Alan Prem Kumar, Kwang Seok Ahn, Gautam Sethi, Manikandan Lakshmanan
Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation...
February 16, 2018: Oncotarget
Jie Zhou, Wei Xiang, Shenjie Li, Qi Hu, Tao Peng, Ligang Chen, Yang Ming
The incidence rate of gliomas is the highest among primary brain tumors. Although the understanding of the molecular pathology of glioma has improved during the previous two decades, effective therapies are not yet available to treat these tumors. Previous studies have indicated that long non-coding RNAs (lncRNAs) have a close association with glioma, suggesting that lncRNAs may be potential targets for the development of novel treatments for glioma. The present review summarized the latest studies on the dysregulation of lncRNAs in glioma, and discussed their potential use in the diagnosis, prognosis and therapies of glioma...
April 2018: Oncology Letters
Benjamin A Farber, Gadi Lalazar, Elana P Simon, William J Hammond, David Requena, Umesh K Bhanot, Michael P La Quaglia, Sanford M Simon
Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer found in adolescents and young adults without underlying liver disease. A deletion of ~400 kD has been found in one copy of chromosome 19 in the tumor tissue of all patients tested. This produces a fusion of the genes DNAJB1 and PRKACA which, in turn, produces a chimeric transcript and protein. Transcriptomic analysis of the tumor has shown upregulation of various oncologically relevant pathways, including EGF/ErbB, Aurora Kinase A, pak21 and wnt...
February 13, 2018: Oncotarget
Guohong Liu, Francois X Claret, Fuling Zhou, Yunbao Pan
C-Jun activation domain-binding protein-1 (Jab1) involves in controlling cellular proliferation, cell cycle, apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage response (DDR). Jab1/COPS5 dysregulation contributes to oncogenesis by deactivating several tumor suppressors and activating oncogenes. Jab1 overexpression was found in many tumor types, illuminating its important role in cancer initiation, progression, and prognosis. Jab1/COPS5 has spurred a strong research interest in developing inhibitors of oncogenes/oncoproteins for cancer therapy...
2018: Frontiers in Pharmacology
Jinghua Liu, Zhen Yu, Yuanyuan Xiao, Qiong Meng, Yeying Wang, Wei Chang
Background: The Forkhead transcription family member FOXA2 plays a fundamental role in hepatocellular carcinoma (HCC) progression, but the precise interaction factor and molecular regulation of FOXA2 are not fully understood. Objective: In this study, we found that FOXA2 could interact with sirtuin 6 (SIRT6) directly in vivo and in vitro. We explored that the expressions of FOXA2 and SIRT6 were significantly downregulated in human HCC and HCC cell lines. Methods: Functionally, cell counting kit-8 assay and Transwell® assay were performed; we demonstrated that the knockdown of FOXA2 and SIRT6 promoted HepG2 cells and Huh7 cells proliferation and invasion in vitro...
2018: Cancer Management and Research
Carla Danussi, Promita Bose, Prasanna T Parthasarathy, Pedro C Silberman, John S Van Arnam, Mark Vitucci, Oliver Y Tang, Adriana Heguy, Yuxiang Wang, Timothy A Chan, Gregory J Riggins, Erik P Sulman, Frederick Lang, Chad J Creighton, Benjamin Deneen, C Ryan Miller, David J Picketts, Kasthuri Kannan, Jason T Huse
Mutational inactivation of the SWI/SNF chromatin regulator ATRX occurs frequently in gliomas, the most common primary brain tumors. Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear, despite its recent implication in both genomic instability and telomere dysfunction. Here we report that Atrx loss recapitulates characteristic disease phenotypes and molecular features in putative glioma cells of origin, inducing cellular motility although also shifting differentiation state and potential toward an astrocytic rather than neuronal histiogenic profile...
March 13, 2018: Nature Communications
J Wu, H Zhang, W Zhang, J Zhang, X Lin, G Xue, F Gao
Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogen- esis, proliferation, invasion, migration and apoptosis in multiple malignant tumors. However, the roles of TFF3 concerning the viability, migration and invasion in papillary thyroid carcinoma cells have not yet been studied. This study aimed to investigate the effect of TFF3 knockdown on a thyroid papillary carcinoma TPC-1 cell line both in vitro and in vivo. In the present study, lentivirus-mediated short hairpin RNA (shRNA) targeting TFF3 plasmids were first constructed and stable TPC-1 cells were obtained while their TFF3 gene was silenced with either shTFF3-TPC-1, or a scrambled shRNA control...
2018: Neoplasma
Jaclyn Andricovich, Stephanie Perkail, Yan Kai, Nicole Casasanta, Weiqun Peng, Alexandros Tzatsos
KDM6A, an X chromosome-encoded histone demethylase and member of the COMPASS-like complex, is frequently mutated in a broad spectrum of malignancies and contributes to oncogenesis with poorly characterized mechanisms. We found that KDM6A loss induced squamous-like, metastatic pancreatic cancer selectively in females through deregulation of the COMPASS-like complex and aberrant activation of super-enhancers regulating ΔNp63, MYC, and RUNX3 oncogenes. This subtype of tumor developed in males had concomitant loss of UTY and KDM6A, suggesting overlapping roles, and points to largely demethylase independent tumor suppressor functions...
March 12, 2018: Cancer Cell
Fanxin Zeng, Xiao Chen, Weiyi Cui, Wei Wen, Fujian Lu, Xueting Sun, Dongwei Ma, Ye Yuan, Zezhong Li, Ning Hou, Hong Zhao, Xinyu Bi, Jianjun Zhao, Jianguo Zhou, Yan Zhang, Rui-Ping Xiao, Jianqiang Cai, Xiuqin Zhang
The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer (CRC) and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation...
March 12, 2018: Cancer Research
Marcel Wiesweg, Henning Reis, Tobias Köster, Moritz Goetz, Karl Worm, Thomas Herold, Andreas Paul, Alexander Dechêne, Brigitte Schumacher, Peter Markus, Isabel Virchow, Karina Kostbade, Nathalie Wolf, Gregor Zaun, Martin Metzenmacher, Kurt W Schmid, Martin Schuler, Stefan Kasper
BACKGROUND: Deregulation of signal transduction pathways plays a critical role in oncogenesis of colorectal cancer (CRC) and directly affects sensitivity to targeted therapies. Against this background we developed a comprehensive biomarker profiling program including markers of downstream signaling to study their association with clinical outcomes. PATIENTS AND METHODS: A prospectively studied cohort of 160 patients with metastatic CRC was included. Standard diagnostic workup included mutational analyses of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
February 17, 2018: Clinical Colorectal Cancer
Ricardo Leão, Joana Dias Apolónio, Donghyun Lee, Arnaldo Figueiredo, Uri Tabori, Pedro Castelo-Branco
BACKGROUND: Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. MAIN BODY: The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability...
March 12, 2018: Journal of Biomedical Science
Alessia Gallo, Monica Miele, Ester Badami, Pier Giulio Conaldi
Patients following solid organ transplantation show a higher risk of developing cancer compared to the general population. Elevated risk is likely due to the interplay of a combination of factors, such as chronic inflammation, coexisting medical conditions, immunosuppressive regimen and persistent infection with oncogenic viruses. In addition, the tumor microenvironment plays a pivotal role in cancer progression, by driving recruitment and in situ differentiation of anti-inflammatory cells of the adaptive and innate immune system such as regulatory T cells, Th17, Dendritic Cells, Myeloid Derived Suppressor Cells, Type 2 Macrophages...
February 16, 2018: Cellular Immunology
Z Wyżewski, K P Gregorczyk, J Szczepanowska, L Szulc-Dąbrowska
Heat shock proteins (Hsps) are a family of proteins highly conserved in evolution. Members of the Hsp family are mainly responsible for proper protein folding, however they perform many other functions in living organisms. Hsp60 is a molecular chaperone that is present in mitochondria and cytosol of eukaryotic cells, as well as on their surface. It is also found in the extracellular space and in the peripheral blood. Apart from its role in assisting protein folding in cooperation with Hsp10, Hsp60 contributes to regulation of apoptosis, as well as participates in modulation of the immune system activity...
2018: Acta Virologica
Agnieszka Barchnicka, Małgorzata Olejniczak-Nowakowska, Karolina Krupa-Kotara, Sebastian Grosicki
Angiogenesis plays a significant role in oncogenesis, and thus it has become an attractive target for cancer treatment. It is the formation of new blood vessels that occurs physiologically as well as under pathological conditions, and may influence cancer proliferation and survival. The current therapeutic approach in oncology includes conventional chemotherapy in combination with biologically-based treatment in various perspectives, targeting not only the malignant cells, but also its microenvironment. Target treatment might be less toxic than conventional chemotherapy...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
V Petrosino, G Motta, G Tenore, M Coletta, A Guariglia, D Testa
Previous literature has highlighted the mechanisms of molecular toxicity induced by substances such as arsenic, cadmium, chromium, nickel, lead, barium and PCBs. The research was carried out on 20 volunteers, all the patients gave their consent to the research: the aim of the study was to evaluate the presence of metals and PCBs in these different matrices (blood and hair), correlating the biochemical data to pathological conditions present, and also to the area in which patients resided. Various quantitative determinations were carried out on samples of blood and hair for 14 heavy metals and on blood samples for 12 PCBs...
March 8, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Sergio Rivas, Carla Gómez-Oro, Inés M Antón, Francisco Wandosell
The cancer stem cell (CSC) hypothesis suggests that tumours are maintained by a subpopulation of cells with stem cell properties. Although the existence of CSCs was initially described in human leukaemia, less evidence exists for CSCs in solid tumours. Recently, a CD133+ cell subpopulation was isolated from human brain tumoursexhibiting stem cell properties in vitro as well as the capacity to initiate tumours in vivo. In the present work, we try to summarize the data showing that some elements of the Phosphoinositide 3-kinase Class I (PI3K)/ Thymoma viral oncogene protein kinase (Akt) pathway, such the activity of PI3K Class I or Akt2, are necessary to maintain the CSC-like phenotype as well as survival of CSCs (also denoted as tumour-initiating cells (TICs))...
March 7, 2018: Biomedicines
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