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cancer proteomics

Hui-I Yu, Hsiu-Chuan Chou, Yi-Ching Su, Li-Hsun Lin, Chieh-Hsiang Lu, Hsiang-Hsun Chuang, Yi-Ting Tsai, En-Chi Liao, Yu-Shan Wei, Yi-Ting Yang, Ying-Ray Lee, Hong-Lin Chan
Evodiamine is a natural product extracted from herbal plants such as Tetradium which has shown to have anti-fat uptake and anti-proliferation properties. However, the effects of evodiamine on the behavior of thyroid cancers are largely unknown. To determine if evodiamine might be useful in the treatment of thyroid cancer and its cytotoxic mechanism, we analyzed the impact of evodiamine treatment on differential protein expression in human thyroid cancer cell line ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS)...
August 9, 2018: Journal of Pharmaceutical and Biomedical Analysis
Wen Wen Xu, Can-Can Zheng, Yunna Huang, Wen-You Chen, Qing-Sheng Yang, Jia-Yi Ren, Yue-Ming Wang, Qing-Yu He, Hua-Xin Liao, Bin Li
A library consisting of 429 food-source compounds was used to screen the natural products with anticancer property in esophageal squamous cell carcinoma (ESCC). We demonstrated for the first time that synephrine, an active compound isolated from leaves of citrus trees, markedly suppressed cell proliferation (Inhibition rate with 20 µM synephrine at day 5: 71.1 ± 5.8% and 75.7 ± 6.2% for KYSE30 and KYSE270, respectively) and colony formation (Inhibition rate with 10 µM synephrine: 86.5 ± 5.9% and 82.3 ± 4...
August 16, 2018: Journal of Agricultural and Food Chemistry
E F Gaffney, P H Riegman, W E Grizzle, P H Watson
The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE) archival pathology material may be dictated by the cancer research question or analytical technique, or may be governed by national ethical, legal and social implications (ELSI), biobank, and sample availability and access policy. Biobanked samples of common tumors are likely to be available, but not all samples will be annotated with treatment and outcomes data and this may limit their application. Tumors that are rare or very small exist mostly in FFPE pathology archives...
August 16, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Mam Y Mboge, Anusha Kota, Robert McKenna, Susan C Frost
Carbonic anhydrases (CAs) are thought to be important for regulating pH in the tumor microenvironment. A few of the CA isoforms are upregulated in cancer cells, with only limited expression in normal cells. For these reasons, there is interest in developing inhibitors that target these tumor-associated CA isoforms, with increased efficacy but limited nonspecific cytotoxicity. Here we present some of the biophysical, biochemical, and cell based techniques and approaches that can be used to evaluate the potency of CA targeted inhibitors and decipher the role of CAs in tumorigenesis, cancer progression, and metastatic processes...
2018: International Journal of Medicinal Chemistry
Diego Sbrissa, Louie Semaan, Barani Govindarajan, Yanfeng Li, Nicholas J Caruthers, Paul M Stemmer, Michael L Cher, Seema Sethi, Ulka Vaishampayan, Assia Shisheva, Sreenivasa R Chinni
Chemokine signaling regulates cell migration and tumor metastasis. CXCL12, a member of the chemokine family, and its receptor, CXCR4, a G protein coupled receptor (GPCR), are key mediators of prostate-cancer (PC) bone metastasis. In PC cells androgens activate CXCR4 gene expression and receptor signaling on lipid rafts, which induces protease expression and cancer cell invasion. To identify novel lipid-raft-associated CXCR4 regulators supporting invasion/metastasis, we performed a SILAC-based quantitative proteomic analysis of lipid-rafts derived from PC3 stable cell lines with overexpression or knockdown of CXCR4...
August 15, 2018: Oncogene
Minghui Yang, Jingli Tao, Hao Wu, Lu Zhang, Yujun Yao, Lixi Liu, Tianqi Zhu, Hao Fan, Xudai Cui, Haoran Dou, Guoshi Liu
The anti-inflammatory activity of melatonin (MT) has been well documented; however, little is known regarding endogenously occurring MT in this respect, especially for large animals. In the current study, we created a MT-enriched animal model (goats) overexpressing the MT synthetase gene Aanat . The responses of these animals to lipopolysaccharide (LPS) stimulation were systematically studied. It was found that LPS treatment exacerbated the inflammatory response in wild-type (WT) goats and increased their temperature to 40 °C...
August 15, 2018: International Journal of Molecular Sciences
E Besray Unal, Christina Kiel, Hannah Benisty, Andrew Campbell, Karen Pickering, Nils Blüthgen, Owen J Sansom, Luis Serrano
BACKGROUND: Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant. METHODS: We performed Spearman's rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue...
August 15, 2018: Cell Communication and Signaling: CCS
Virgínea de Araujo Farias, Francisco O'Valle, Santiago Serrano-Saenz, Per Anderson, Eduardo Andrés, Jesús López-Peñalver, Isabel Tovar, Ana Nieto, Ana Santos, Francisco Martín, José Expósito, F Javier Oliver, José Mariano Ruiz de Almodóvar
BACKGROUND: We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). METHODS: We have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment...
August 15, 2018: Molecular Cancer
Martin H Pedersen, Brian L Hood, Sidse Ehmsen, Hans C Beck, Thomas P Conrads, Martin Bak, Henrik J Ditzel, Rikke Leth-Larsen
Prognostic and predictive biomarkers of disease and treatment outcome are needed to ensure optimal treatment of patients with TNBC. In a mass spectrometry-based global proteomic study of 44 formalin-fixed, paraffin-embedded (FFPE) primary TNBC tumors and 10 corresponding metastases, we found that Cytochrome P450 reductase (CYPOR) expression correlated with patient outcome. The correlation between CYPOR expression and outcome was further evaluated in a Danish cohort of 113 TNBC patients using immunohistochemistry and publicly available gene expression data from two cohorts of TNBC and basal-like breast cancer patients, respectively (N=249 and N=580)...
August 15, 2018: International Journal of Cancer. Journal International du Cancer
Thomas F Gronauer, Melanie M Mandl, Markus Lakemeyer, Mathias W Hackl, Martina Meßner, Vadim S Korotkov, Johanna Pachmayr, Stephan A Sieber
Human caseinolytic protease P (hClpP) is important for degradation of misfolded proteins in the mitochondrial unfolded protein response. We here introduce tailored hClpP inhibitors that utilize a steric discrimination in their core naphthofuran scaffold to selectively address the human enzyme. This novel inhibitor generation exhibited superior activity compared to previously introduced beta-lactones, optimized for bacterial ClpP. Further insights into the bioactivity and binding to cellular targets were obtained via chemical proteomics as well as proliferation- and migration studies in cancer cells...
August 15, 2018: Chemical Communications: Chem Comm
Jun Cheng, Li-Ming Wu, Xue-Song Deng, Jian Wu, Zhen Lv, Hang-Fen Zhao, Zhang Yang, Yong Ni
BACKGROUND: Accumulating evidence demonstrates that microRNAs (miRNAs) play essential roles in tumorigenesis and cancer progression of hepatocellular carcinoma (HCC). Average targets of a miRNA were more than 100. And one miRNA may act in tumor via regulating several targets. The present study aimed to explore more potential targets of miR-449a by proteomics technology and further uncover the role of miR-449a in HCC tumorigenesis. METHODS: Technologies such as iTRAQ-based quantitative proteomic were used to investigate the effect of miR-449a on HCC...
July 26, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Yu Shi, Zuhua Chen, Juanjuan Gao, Si Wu, Haer Gao, Guoshuang Feng
Alternative mRNA splicing (AS) contributes greatly to expanding the diversity and function of the proteome. Increasing evidence has suggested that dysregulation of mRNA splicing may be associated with various types of cancer. In the present study, RNA sequencing data were used to investigate alterations to the global mRNA splicing landscape of cellular genes from 452 stomach adenocarcinoma (STAD) tissues available in The Cancer Genome Atlas. Seven types of AS events, including the profiles of exon skipping events, were analyzed using SpliceSeq software...
August 2, 2018: Oncology Reports
Kalliopi I Pappa, Polyxeni Christou, Amarildo Xholi, George Mermelekas, Georgia Kontostathi, Vasiliki Lygirou, Manousos Makridakis, Jerome Zoidakis, Nicholas P Anagnou
The available therapeutic approaches for cervical cancer can seriously affect the fertility potential of patient; thus, there is a pressing requirement for less toxic and targeted therapies. The membrane proteome is a potential source of therapeutic targets; however, despite the significance of membrane proteins in cancer, proteomic analysis has been a challenging task due to their unique biochemical properties. The aim of the present study was to develop an efficient membrane protein enrichment protocol, and to the best of our knowledge, to compare for the first time the expression pattern of membrane proteins of one normal cell line, HCK1T, and three cervical cancer cell lines, C33A, a human papilloma virus (HPV)-negative cell line, and two HPV-positive cell lines, SiHa (HPV16+) and HeLa (HPV18+)...
August 7, 2018: International Journal of Oncology
Yukihiro Furusawa, Tatsuya Yunoki, Tetsushi Hirano, Satsuki Minagawa, Hironori Izumi, Hisashi Mori, Atsushi Hayashi, Yoshiaki Tabuchi
Bcl‑2‑associated athanogene (BAG) 3, is a member of the BAG protein family and a known co‑chaperone of heat shock protein (HSP) 70. BAG3 serves a role in regulating a variety of cellular functions, including cell growth, proliferation and cell death including apoptosis. BAG3 is a stress‑inducible protein, however the constitutive expression level of BAG3 is increased in cancer cells compared with healthy cells. Recent proteomics technology combined with bioinformatics has revealed that BAG3 participates in an interactome with a number of proteins other than its typical partner HSP70...
August 10, 2018: Molecular Medicine Reports
Han Yao, Huanbin Wang, Chushu Li, Jing-Yuan Fang, Jie Xu
Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are responsible for delivering inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells. However, recent studies revealed intrinsic expression of PD-1 in melanoma and some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1 expressed by tumor cells, modulating downstream mammalian target of rapamycin signaling and promoting tumor growth independent of adaptive immunity...
2018: Frontiers in Immunology
Xia Wang, Roope A Kallionpää, Patrick R Gonzales, Dhananjay A Chitale, Renee N Tousignant, Jacob P Crowley, Zhihua Chen, Sean J Yoder, Jaishri O Blakeley, Maria T Acosta, Bruce R Korf, Ludwine M Messiaen, Michael A Tainsky
NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been proposed as oncogenic drivers in sporadic breast cancers. To understand the genomic and histological characteristics of these breast cancers, we analyzed the tumors with NF1 germline mutations and also examined the genomic and proteomic profiles of unselected tumors. Among 14 breast cancer specimens from 13 women affected with neurofibromatosis type 1 (NF1), 9 samples (NF+BrCa) underwent genomic copy number (CN) and targeted sequencing analysis...
August 13, 2018: Cancer Prevention Research
Qingqing Wang, Donald C Rio
Alternative pre-mRNA splicing (AS) greatly diversifies metazoan transcriptomes and proteomes and is crucial for gene regulation. Current computational analysis methods of AS from Illumina RNA-sequencing data rely on preannotated libraries of known spliced transcripts, which hinders AS analysis with poorly annotated genomes and can further mask unknown AS patterns. To address this critical bioinformatics problem, we developed a method called the junction usage model (JUM) that uses a bottom-up approach to identify, analyze, and quantitate global AS profiles without any prior transcriptome annotations...
August 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Zhichang Yang, Xiaojing Shen, Daoyang Chen, Liangliang Sun
Capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) has been well recognized for bottom-up proteomics. It has approached 4000-8000 protein identifications (IDs) from a human cell line, mouse brains or Xenopus embryos via coupling with liquid chromatography (LC) prefractionation. However, at least five hundred micrograms of complex proteome digests were required for the LC-CZE-MS/MS studies. This requirement of a large amount of initial peptide material impedes the application of CZE-MS/MS for deep bottom-up proteomics of mass-limited samples...
August 13, 2018: Analytical Chemistry
Hanibal Bohnenberger, Lars Kaderali, Philipp Ströbel, Diego Yepes, Uwe Plessmann, Neekesh V Dharia, Sha Yao, Carina Heydt, Sabine Merkelbach-Bruse, Alexander Emmert, Jonatan Hoffmann, Julius Bodemeyer, Kirsten Reuter-Jessen, Anna-Maria Lois, Leif Hendrik Dröge, Philipp Baumeister, Christoph Walz, Lorenz Biggemann, Roland Walter, Björn Häupl, Federico Comoglio, Kuan-Ting Pan, Sebastian Scheich, Christof Lenz, Stefan Küffer, Felix Bremmer, Julia Kitz, Maren Sitte, Tim Beißbarth, Marc Hinterthaner, Martin Sebastian, Joachim Lotz, Hans-Ulrich Schildhaus, Hendrik Wolff, Bernhard C Danner, Christian Brandts, Reinhard Büttner, Martin Canis, Kimberly Stegmaier, Hubert Serve, Henning Urlaub, Thomas Oellerich
Patients with head-and-neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types...
August 10, 2018: EMBO Molecular Medicine
Huan Liu, Siying Li, Xiaohui Liu, Yuling Chen, Haiteng Deng
SIRT3 is a NAD+-dependent mitochondrial protein deacetylase implicated in the regulation of central metabolism and mitochondrial proteostasis. SIRT3 is downregulated in clear cell renal cell carcinoma (ccRCC), which is the most common form of renal cancer. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction and elevated fat deposition, it is unknown whether SIRT3 plays a role in tumorigenesis and the development of this disease. In the present study, we found that SIRT3 overexpression and knockdown had opposing effects on the growth of ccRCC cells, decreasing and increasing the rate of cell proliferation, respectively...
August 10, 2018: Journal of Proteome Research
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