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Rui Huang, Huimin Liu, Yiran Chen, Yanjie He, Qian Kang, Sanfang Tu, Yingzhi He, Xuan Zhou, Lei Wang, Jilong Yang, Anqin Wu, Yuhua Li
Although the introduction of tyrosine kinase inhibitors greatly improved the survival of patients with chronic myeloid leukemia (CML), drug resistance remains a problem. Thus, mechanism-based novel therapeutic targets warrant exploration. Recently, epidermal growth factor receptor kinase substrate 8 (EPS8), which has been identified as an oncogene and plays an important role in a broad spectrum of solid tumours, was reported to be related to poor prognosis or chemoresistance in acute leukemia patients. However, its role in CML remains unclear...
January 2018: Oncology Reports
Elham Nasri, Lisa B Wiesen, Jacquelyn A Knapik, Kristianna M Fredenburg
In vitro head and neck cancer studies have demonstrated that epidermal growth factor receptor kinase substrate 8 (Eps8) overexpression contributes to squamous carcinogenesis. Oral squamous cell carcinoma studies have correlated Eps8 expression with metastatic disease and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) studies comparing its expression by anatomic site or in in vivo regional metastases have not been performed. In this study, we compared Eps8 expression in HNSCCs arising in the oral cavity (OCSCC) and oropharynx (OPSCC) along with their corresponding regional lymph nodes (LNs) metastases...
October 28, 2017: Human Pathology
Linxi Li, Elizabeth I Tang, Haiqi Chen, Qingquan Lian, Renshan Ge, Bruno Silvestrini, C Yan Cheng
The mechanism that regulates sperm release at spermiation is unknown. Herein, we utilized an animal model wherein rats were treated with adjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide, via oral gavage to induce premature release of elongating/elongated spermatid, followed by round spermatids and spermatocytes. Spermatid release mimicking spermiation occurred within 6-12 h following adjudin treatment and by 96 h, virtually all tubules were devoid of spermatids. Using this model, we tracked the organization of F-actin and microtubules (MTs) by immunofluorescence microscopy, and the association of actin or MT regulatory proteins that either promote or demolish cytoskeletal integrity through changes in the organization of actin-microfilaments or MTs by co-immunoprecipitation...
October 12, 2017: Endocrinology
Christof Litschko, Joern Linkner, Stefan Brühmann, Theresia E B Stradal, Tobias Reinl, Lothar Jänsch, Klemens Rottner, Jan Faix
The WAVE regulatory complex (WRC) links upstream Rho-family GTPase signaling to the activation of the ARP2/3 complex in different organisms. WRC-induced and ARP2/3 complex-mediated actin nucleation beneath the plasma membrane is critical for actin assembly in the leading edge to drive efficient cell migration. The WRC is a stable heteropentamer composed of SCAR/WAVE, Abi, Nap, Pir and the small polypeptide Brk1/Hspc300. Functional interference with individual subunits of the complex frequently results in diminished amounts of the remaining polypeptides of the WRC complex, implying the complex to act as molecular entity...
September 4, 2017: European Journal of Cell Biology
Niranjan Jeganathan, Dan Predescu, Sanda Predescu
Intersectin-1s (ITSN-1s), a multidomain adaptor protein, plays a vital role in endocytosis, cytoskeleton rearrangement and cell signaling. Recent studies have demonstrated that deficiency of ITSN-1s is a crucial early event in pulmonary pathogenesis. In lung cancer, ITSN-1s deficiency impairs Eps8 ubiquitination and favors Eps8-mSos1 interaction which activates Rac1 leading to enhanced lung cancer cell proliferation, migration and metastasis. Restoring ITSN-1s deficiency in lung cancer cells facilitates cytoskeleton changes favoring mesenchymal to epithelial transformation and impairs lung cancer progression...
September 6, 2017: Respiratory Research
Jo Tod, Christopher J Hanley, Mark R Morgan, Marta Rucka, Toby Mellows, Maria-Antoinette Lopez, Philip Kiely, Karwan A Moutasim, Steven J Frampton, Durgagauri Sabnis, David R Fine, Colin Johnson, John F Marshall, Giorgio Scita, Veronika Jenei, Gareth J Thomas
The integrin αvβ6 is up-regulated in numerous carcinomas, where expression commonly correlates with poor prognosis. αvβ6 promotes tumour invasion, partly through regulation of proteases and cell migration, and is also the principal mechanism by which epithelial cells activate TGF-β1; this latter function complicates therapeutic targeting of αvβ6, since TGF-β1 has both tumour-promoting and -suppressive effects. It is unclear how these different αvβ6 functions are linked; both require actin cytoskeletal reorganization, and it is suggested that tractive forces generated during cell migration activate TGF-β1 by exerting mechanical tension on the ECM-bound latent complex...
September 2017: Journal of Pathology
Xiaoping Wu, Bernt Guldbrandtsen, Ulrik Sander Nielsen, Mogens Sandø Lund, Goutam Sahana
Identification of the genetic variants associated with calf survival in dairy cattle will aid in the elimination of harmful mutations from the cattle population and the reduction of calf and young stock mortality rates. We used de-regressed estimated breeding values for the young stock survival (YSS) index as response variables in a genome-wide association study with imputed whole-genome sequence variants. A total of 4,610 bulls with estimated breeding values were genotyped with the Illumina BovineSNP50 (Illumina, San Diego, CA) single nucleotide polymorphism (SNP) genotyping array...
May 24, 2017: Journal of Dairy Science
Ying Gao, Haiqi Chen, Wing-Yee Lui, Will M Lee, C Yan Cheng
A local axis connects the apical ectoplasmic specialization (ES) at the Sertoli-spermatid interface, the basal ES at the blood-testis barrier (BTB), and the basement membrane across the seminiferous epithelium functionally in rat testes. As such, cellular events that take place simultaneously across the epithelium such as spermiation and BTB remodeling that occur at the apical ES and the basal ES, respectively, at stage VIII of the cycle are coordinated. Herein, laminin α2, a structural component of the basement membrane, was found to regulate BTB dynamics...
April 1, 2017: Endocrinology
Won-Sik Shin, Hyun Jae Shim, Young Hun Lee, Minju Pyo, Jun Sang Park, So Yun Ahn, Seung-Taek Lee
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma---membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells...
September 2017: Journal of Cellular Biochemistry
Yin Lu, Jianshe Wang, Xuejiang Guo, Shengmin Yan, Jiayin Dai
Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0...
March 1, 2017: Toxicology and Applied Pharmacology
Elise Delage, Diégo Cordero Cervantes, Esthel Pénard, Christine Schmitt, Sylvie Syan, Andrea Disanza, Giorgio Scita, Chiara Zurzolo
Tunneling Nanotubes (TNTs) are actin enriched filopodia-like protrusions that play a pivotal role in long-range intercellular communication. Different pathogens use TNT-like structures as "freeways" to propagate across cells. TNTs are also implicated in cancer and neurodegenerative diseases, making them promising therapeutic targets. Understanding the mechanism of their formation, and their relation with filopodia is of fundamental importance to uncover their physiological function, particularly since filopodia, differently from TNTs, are not able to mediate transfer of cargo between distant cells...
December 23, 2016: Scientific Reports
Sai Huang, Cong Feng, Li Chen, Zhi Huang, Xuan Zhou, Bei Li, Li-Li Wang, Wei Chen, Fa-Qin Lv, Tan-Shi Li
BACKGROUND This study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq). MATERIAL AND METHODS A total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE-lncRNAs were predicted, and the regulatory network was constructed...
September 24, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Niranjan Jeganathan, Dan Predescu, Jin Zhang, Fei Sha, Cristina Bardita, Monal Patel, Stephen Wood, Jeffrey A Borgia, Robert A Balk, Sanda Predescu
BACKGROUND: The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. METHODS: Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies...
September 14, 2016: Molecular Cancer
D Fang, H Chen, J Y Zhu, W Wang, Y Teng, H-F Ding, Q Jing, S-B Su, S Huang
Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells...
March 2017: Oncogene
Qian Li, Wei Bao, Qiong Fan, Wen-Jing Shi, Zhu-Nan Li, Ying Xu, Dan Wu
Epidermal growth factor receptor pathway substrate 8 (Eps8) has been identified as a novel substrate for epidermal growth factor receptor (EGFR) kinase and is involved in EGFR‑mediated signaling pathways correlated with tumorigenesis, proliferation and metastasis in various cancer types. However, the precise role of Eps8 in cervical cancer metastasis remains to be elucidated. Immunohistochemistry revealed that Eps8 was significantly increased in cervical cancer specimens compared with squamous intraepithelial lesion and normal cervical tissues...
October 2016: Molecular Medicine Reports
Yu-Ting Wang, Chiung-Chun Huang, Yun-Shan Lin, Weu-Fang Huang, Cheng-Yi Yang, Cheng-Che Lee, Che-Ming Yeh, Kuei-Sen Hsu
Epidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein involved in actin cytoskeleton regulation and is abundantly expressed in many brain regions. However, the functional significance of Eps8 in the brain has only just begun to be elucidated. Here, we demonstrate that genetic deletion of Eps8 (Eps8(-/-)) from excitatory neurons leads to impaired performance in a novel object recognition test. Consistently, Eps8(-/-) mice displayed a deficit in the maintenance of long-term potentiation in the CA1 region of hippocampal slices, which was rescued by bath application of N-methyl-d-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonopentanoate...
January 2017: Neuropharmacology
Ying Gao, Wing-Yee Lui, Will M Lee, C Yan Cheng
Crumbs homolog 3 (or Crumbs3, CRB3) is a polarity protein expressed by Sertoli and germ cells at the basal compartment in the seminiferous epithelium. CRB3 also expressed at the blood-testis barrier (BTB), co-localized with F-actin, TJ proteins occludin/ZO-1 and basal ES (ectoplasmic specialization) proteins N-cadherin/β-catenin at stages IV-VII only. The binding partners of CRB3 in the testis were the branched actin polymerization protein Arp3, and the barbed end-capping and bundling protein Eps8, illustrating its possible role in actin organization...
2016: Scientific Reports
Jing-Wen Du, Yu-Xin Wang, Wei-Jun Zhou, Chun-Jun Jiang, Xiao-Ling Xie, Hong-Hao Zhang, Yan-Jie He, Yu-Hua Li
OBJECTIVE: To find and identify HLA-A*0201 restricted cytotoxic T lymphocyte (CTL) epitopes from epidermal growth factor pathway substrate number 8 (Eps8) for specific immunotherapy based on Eps8-derived epitopes in clinic. METHODS: Online biological softwares involved C-proteasomal cleavage, MHC class I binding affinity and TAP transport efficiency were used for prediction of HLA-A*0201 restricted epitopes from Eps8. Then, T2-binding assays and peptide/MHC complex stability tests were used to further verify the predicted epitopes...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Thankiah Sudhaharan, Kai Ping Sem, Hwi Fen Liew, Yuan Hong Yu, Wah Ing Goh, Ai Mei Chou, Sohail Ahmed
Rif induces dorsal filopodia but the signaling pathway responsible for this has not been identified. We show here that Rif interacts with the I-BAR family protein IRTKS (also known as BAIAP2L1) through its I-BAR domain. Rif also interacts with Pinkbar (also known as BAIAP2L2) in N1E-115 mouse neuroblastoma cells. IRTKS and Rif induce dorsal membrane ruffles and filopodia. Dominant-negative Rif inhibits the formation of IRTKS-induced morphological structures, and Rif activity is blocked in IRTKS-knockout (KO) cells...
July 15, 2016: Journal of Cell Science
Mathew D Littlejohn, Kathryn Tiplady, Tania A Fink, Klaus Lehnert, Thomas Lopdell, Thomas Johnson, Christine Couldrey, Mike Keehan, Richard G Sherlock, Chad Harland, Andrew Scott, Russell G Snell, Stephen R Davis, Richard J Spelman
The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed. To investigate this QTL in detail, we report genome sequence-based imputation and association mapping in a population of 64,244 taurine cattle...
2016: Scientific Reports
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