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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/28821767/identification-of-candidate-genes-for-devil-facial-tumour-disease-tumourigenesis
#1
Robyn L Taylor, Yiru Zhang, Jennifer P Schöning, Janine E Deakin
Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#2
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28805349/crispr-assisted-receptor-deletion-reveals-distinct-roles-for-erbb2-and-erbb3-in-skin-keratinocytes
#3
Maik Dahlhoff, Nadege Gaborit, Sebastian Bultmann, Heinrich Leonhardt, Yosef Yarden, Marlon R Schneider
While the epidermal growth factor receptor (EGFR) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors ERBB2 and ERBB3 in this tissue have only recently been examined. Previously reported, skin-specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both ERBB2 and ERBB3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes...
August 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#4
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28754852/molecular-characterization-of-circulating-colorectal-tumor-cells-defines-genetic-signatures-for-individualized-cancer-care
#5
Say Li Kong, Xingliang Liu, Nur-Afidah Mohamed Suhaimi, Kenneth Jia Hao Koh, Min Hu, Daniel Yoke San Lee, Igor Cima, Wai Min Phyo, Esther Xing Wei Lee, Joyce A Tai, Yu Miin Foong, Jess Honganh Vo, Poh Koon Koh, Tong Zhang, Jackie Y Ying, Bing Lim, Min-Han Tan, Axel M Hillmer
Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28750640/impact-of-somatic-pi3k-pathway-and-erbb-family-mutations-on-pathological-complete-response-pcr-in-her2-positive-breast-cancer-patients-who-received-neoadjuvant-her2-targeted-therapies
#6
Sinead Toomey, Alexander J Eustace, Joanna Fay, Katherine M Sheehan, Aoife Carr, Malgorzata Milewska, Stephen F Madden, Ausra Teiserskiene, Elaine W Kay, Norma O'Donovan, William Gallagher, Liam Grogan, Oscar Breathnach, Janice Walshe, Catherine Kelly, Brian Moulton, M John Kennedy, Guiseppe Gullo, Arnold D Hill, Colm Power, Deirdre Duke, Niamh Hambly, John Crown, Bryan T Hennessy
BACKGROUND: The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies...
July 27, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28750448/-role-of-the-human-erbb-family-receptors-in-urothelial-carcinoma-of-the-bladder-mrna-expression-status-and-prognostic-relevance
#7
Philipp Erben, Felix Wezel, Ralph Wirtz, Thomas Martini, Doron Stein, Cleo-Aaron Weis, Arndt Hartmann, Christian Bolenz
Background Altered expression of epidermal growth factor (EGF) family (ErbB) receptors in urothelial carcinoma of the urinary bladder (UCB) has been associated with adverse outcomes. Given the limited treatment options in UCB, EGFR and HER2 (ERBB2) represent established therapeutic targets in other entities. We assessed the expression of ErbB family receptors (ERBB1 - 4) on mRNA levels in correlation with histopathological and clinical parameters in patients treated with radical cystectomy (RC). Methods 94 patients (female = 22; male = 72; median age: 66...
August 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#8
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#9
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28670312/cervical-cancer-neoantigen-landscape-and-immune-activity-is-associated-with-human-papillomavirus-master-regulators
#10
Yong Qin, Suhendan Ekmekcioglu, Marie-Andrée Forget, Lorant Szekvolgyi, Patrick Hwu, Elizabeth A Grimm, Amir A Jazaeri, Jason Roszik
Human papillomaviruses (HPVs) play a major role in development of cervical cancer, and HPV oncoproteins are being targeted by immunotherapies. Although these treatments show promising results in the clinic, many patients do not benefit or the durability is limited. In addition to HPV antigens, neoantigens derived from somatic mutations may also generate an effective immune response and represent an additional and distinct immunotherapy strategy against this and other HPV-associated cancers. To explore the landscape of neoantigens in cervix cancer, we predicted all possible mutated neopeptides in two large sequencing data sets and analyzed whether mutation and neoantigen load correlate with antigen presentation, infiltrating immune cell types, and a HPV-induced master regulator gene expression signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#11
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590920/hcarg-commd5-inhibits-erbb-receptor-driven-renal-cell-carcinoma
#12
Hiroyuki Matsuda, Carole G Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet, Johanne Tremblay
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570571/construction-and-analyses-of-the-microrna-target-gene-differential-regulatory-network-in-thyroid-carcinoma
#13
Ying-Ying Kang, Yang Liu, Ming-Li Wang, Min Guo, Yan Wang, Zhi-Feng Cheng
Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#14
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in patients younger than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28514724/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#15
Heng-Heng Yuan, Ying-Nan Yang, Jian-Hua Zhou, Yan-Jing Li, Li-Ying Wang, Jun-Wei Qin, Tao Liu, Zhen-Zhen Li, Qing-Xin Zhou, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Wen-Jie Zhang, Lei Liu, Xiao-Xue Du, Yu Han
The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28469731/integrated-data-analysis-reveals-potential-drivers-and-pathways-disrupted-by-dna-methylation-in-papillary-thyroid-carcinomas
#16
Caroline Moraes Beltrami, Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fabio Albuquerque Marchi, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#17
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#18
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
July 2017: MAbs
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#19
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynaecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28399526/expression-of-the-erbb-family-of-ligands-and-receptors-in-gastric-cancer
#20
Sun-Ju Byeon, Hye Seung Lee, Min-A Kim, Byung Lan Lee, Woo Ho Kim
OBJECTIVE: Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. METHODS: We evaluated the expression levels of various ERBB receptor ligands (i.e...
2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
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