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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
Yi Yang, Na Wu, Zhiyong Wang, Fei Zhang, Ran Tian, Wei Ji, Xiubao Ren, Ruifang Niu
The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation...
October 13, 2016: International Journal of Molecular Sciences
Mirjana Bećarević
Antiphospholipid syndrome (APS) is characterized by thromboses and/or pregnancy losses. Laboratory criterion for the diagnosis of APS is the presence of antiphospholipid antibodies (anticardiolipin, anti-beta2-glycoprotein I (aβ2gpI) and lupus anticoagulant). On the one hand, the latest classification criteria for the diagnosis of APS emphasized that thrombotic manifestations of the syndrome should be without any signs of an inflammatory process, while on the other hand, some recent reports have suggested that APS is a "pro-inflammatory state...
October 4, 2016: Rheumatology International
Zhi-Qin Liu, Xiao-Mei Song, Que-Ting Chen, Ting Liu, Ji-Tao Teng, Kun Zhou, Du-Qiang Luo
BACKGROUND: Metformin is a first-line drug for treating type 2 diabetes mellitus, yet its mechanism remains only partially understood and controversial. In this study we assessed a global gene expression profiling in liver of KKAy mice affected by metformin. This study aimed to identify the novel anti-diabetic mechanisms of metformin. METHODS: After KKAy mice were administered metformin for 5 weeks, the gene changes profile in the livers of KKAy mice were assessed by using the Agilent whole mice genome oligo microarray...
September 3, 2016: Pharmacological Reports: PR
Teresia Kling, Roberto Ferrarese, Darren Ó hAilín, Patrik Johansson, Dieter Henrik Heiland, Fangping Dai, Ioannis Vasilikos, Astrid Weyerbrock, Rebecka Jörnsten, Maria Stella Carro, Sven Nelander
Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes...
September 18, 2016: EBioMedicine
Jau-Song Yu, Yi-Ting Chen, Wei-Fan Chiang, Yung-Chin Hsiao, Lichieh Julie Chu, Lai-Chu See, Chi-Sheng Wu, Hui-Tzu Tu, Hsiao-Wei Chen, Chia-Chun Chen, Wei-Chao Liao, Ya-Ting Chang, Chih-Ching Wu, Che-Yi Lin, Shyun-Yeu Liu, Shu-Ti Chiou, Shu-Li Chia, Kai-Ping Chang, Chih-Yen Chien, Su-Wei Chang, Chee-Jen Chang, John D Young, Chia C Pao, Yu-Sun Chang, Leland H Hartwell
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yuelong Wang, Jiaojiao Deng, Gang Guo, Aiping Tong, Xirui Peng, Haifeng Chen, Jianguo Xu, Yi Liu, Chao You, Liangxue Zhou
Annexin A2 (AnxA2) is a highly conserved Ca2(+)-regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis...
September 17, 2016: Journal of Neuro-oncology
Lixing Zhang, Chao Ge, Fangyu Zhao, Yang Zhang, Xin Wang, Ming Yao, Jinjun Li
Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy. Research data supported that cancer stem cells (CSCs) may be responsible for the chemoresistance, and strategies that suppress CSCs stemness could also inhibit the drug resistance. In this study, we found that NRBP2 expression was downregulated in the CD133+ HCC CSCs. Most adjacent non-cancerous liver tissue analyzed expressed higher level of NRBP2 compared with cancerous tissue in HCC patients, and high NRBP2 expression indicated a better prognosis...
September 7, 2016: Cancer Research
V Salle, J Schmidt, A Smail, C Mazière, M A Conte, A Brulé, J C Mazière, E Cadet, Y E Herpe, P Duhaut
Acquired and inherited thrombophilia have both been reported to be associated with an increased risk of obstetric complications in early or later stages of pregnancy. Annexin A2 (ANXA2) is strongly expressed in vascular and placental tissues and plays a crucial role in fibrinolysis. The aim of the present study was to evaluate the prevalence of antibodies directed against ANXA2 in patients with recurrent miscarriage or obstetric complications. Anti-ANXA2 antibodies (aANXA2) were detected by ELISA in the sera from 46 women with obstetric morbidity, mainly recurrent miscarriage...
August 30, 2016: Journal of Reproductive Immunology
Ann Kari Grindheim, Anni Vedeler
Annexin A2 (AnxA2) is present in multiple cellular compartments and interacts with numerous ligands including calcium, proteins, cholesterol, negatively charged phospholipids and RNA. These interactions are tightly regulated by its post-translational modifications. The levels of AnxA2 and its Tyr23 phosphorylated form (pTyr23AnxA2) are increased in many cancers and the protein is involved in malignant cell transformation, metastasis and angiogenesis. Our previous studies of rat pheochromocytoma (PC12) cells showed that reactive oxygen species (ROS) induce rapid, simultaneous and transient dephosphorylation of nuclear AnxA2, most likely associating with PML bodies, while AnxA2 associated with F-actin at the cell cortex undergoes Tyr23 phosphorylation...
July 2016: Communicative & Integrative Biology
Praveenkumar Shetty, Vidya Shankar Patil, Rajshekar Mohan, Leonard Clinton D'souza, Anil Bapu Bargale, Basavaraj R Patil, Dinesh U S, Vikram Haridas, Shrirang P Kulkarni
BACKGROUND: AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate AnxA2 mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. METHODS: Secretory AnxA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative (n=20) and positive breast cancer patients (n=16)...
August 5, 2016: Annals of Clinical Biochemistry
Isabelle V Leefa Chong San, Gaëlle Prost, Jennifer A Williams, Stephen E Moss, Ulrike A Nuber
Podocalyxin (PODXL) is a highly glycosylated and sialylated transmembrane protein that is up-regulated in various types of tumors and whose expression levels positively correlate with tumor grade. We previously found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells (NSPs). Here we investigated the effects of elevated Podxl levels in these cells. NSPs overexpressing Podxl did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumor initiation...
September 16, 2016: Biochemical and Biophysical Research Communications
Heidi R Fuller, Thomas H Gillingwater, Thomas M Wishart
The neuromuscular disease spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting from low levels of full-length survival motor neuron (SMN) protein. Despite having a good understanding of the underlying genetics of SMA, the molecular pathways downstream of SMN that regulate disease pathogenesis remain unclear. The identification of molecular perturbations downstream of SMN is required in order to fully understand the fundamental biological role(s) for SMN in cells and tissues of the body, as well as to develop a range of therapeutic targets for developing novel treatments for SMA...
September 2016: Neuromuscular Disorders: NMD
R Weiss, A Bitton, L Nahary, M T Arango, I Benhar, M Blank, Y Shoenfeld, J Chapman
Antiphospholipid syndrome (APS) affects coagulation and the brain by autoimmune mechanisms. The major antigen in APS is beta-2-glycoprotein I (β2-GPI) is known to complex with annexin A2 (ANXA2), and antibodies to ANXA2 have been described in APS. We measured these antibodies in mice with experimental APS (eAPS) induced by immunization with β2-GPI. Sera of these mice reacted significantly with recombinant ANXA2 by enzyme-linked immunosorbent assay (ELISA) and the eAPS mice had significantly high levels of immunoglobulin G (IgG) in the brain by immunoblot assays compared to adjuvant immunized controls...
July 23, 2016: Immunologic Research
Francesca Maule, Silvia Bresolin, Elena Rampazzo, Daniele Boso, Alessandro Della Puppa, Giovanni Esposito, Elena Porcù, Stefania Mitola, Giuseppe Lombardi, Benedetta Accordi, Manuela Tumino, Giuseppe Basso, Luca Persano
Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM...
July 13, 2016: Oncotarget
Stefano Rossetti, Wiam Bshara, Johanna A Reiners, Francesca Corlazzoli, Austin Miller, Nicoletta Sacchi
Regardless of the etiological factor, an aberrant morphology is the common hallmark of ductal carcinoma in situ (DCIS), which is a highly heterogeneous disease. To test if critical core morphogenetic mechanisms are compromised by different mutations, we performed proteomics analysis of five mammary epithelial HME1 mutant lines that develop a DCIS-like morphology in three dimensional (3D) culture. Here we show first, that all HME1 mutant lines share a common protein signature highlighting an inverse deregulation of two annexins, ANXA2 and ANXA8...
October 1, 2016: Cancer Letters
Chel Hun Choi, Joon-Yong Chung, Eun Joo Chung, John D Sears, Jeong-Won Lee, Duk-Soo Bae, Stephen M Hewitt
BACKGROUND: The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer. METHODS: ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients...
2016: BMC Cancer
Sisi He, Xuefeng Li, Rongpeng Li, Lizhu Fang, Lingyun Sun, Yongsheng Wang, Min Wu
Sepsis is a progressive disease manifesting excessive inflammatory responses, severe tissue injury, organ dysfunction, and, ultimately, mortality. Since currently, there are limited therapeutic options for this disease, further understanding the molecular pathogenesis of sepsis may help develop effective treatments. Here we identify a novel role for Annexin A2 (AnxA2), a multi-compartmental protein, in inhibiting pro-inflammatory response by regulating reactive oxygen species (ROS) and IL-17 signaling during sepsis...
July 2016: PLoS Pathogens
Chin-Hui Lin, Yao-Wen Lin, Ying-Chun Chen, Chen-Chung Liao, Yuh-Shan Jou, Ming-Ta Hsu, Chian-Feng Chen
Recurrence and metastasis are common in hepatocellular carcinoma (HCC) and correlate with poor prognosis. We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in HCC metastasis. Overexpression of FNDC3B in HCC cell lines enhanced cell migration and invasion. On the other hand, knockdown of FNDC3B using short-hairpin RNA reduced tumor nodule formation in both intra- and extra-hepatic metastasis. High levels of FNDC3B were observed in metastatic HCCs and correlated with poor patient survival and shorter recurrence time...
July 1, 2016: Oncotarget
Shiyu Wang, Hong Sun, Michael Tanowitz, Xue-Hai Liang, Stanley T Crooke
Chemically modified antisense oligonucleotides (ASOs) designed to mediate site-specific cleavage of RNA by RNase H1 are used as research tools and as therapeutics. ASOs modified with phosphorothioate (PS) linkages enter cells via endocytotic pathways. The mechanisms by which PS-ASOs are released from membrane-enclosed endocytotic organelles to reach target RNAs remain largely unknown. We recently found that annexin A2 (ANXA2) co-localizes with PS-ASOs in late endosomes (LEs) and enhances ASO activity. Here, we show that co-localization of ANXA2 with PS-ASO is not dependent on their direct interactions or mediated by ANXA2 partner protein S100A10...
September 6, 2016: Nucleic Acids Research
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