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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#1
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#2
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28036286/her3-and-linc00052-interplay-promotes-tumor-growth-in-breast-cancer
#3
Ahmad Salameh, Xuejun Fan, Byung-Kwon Choi, Shu Zhang, Ningyan Zhang, Zhiqiang An
Here we report that the lncRNA LINC00052 expression correlates positively with HER3/ErbB3 levels in breast cancer cells. Gene silencing of LINC00052 diminished both LINC00052 and HER3 expression and reduced cancer cell growth in vitro and in vivo. LINC00052 overexpression promoted cancer cell growth in vitro and in vivo and increased HER3-mediated downstream signaling. Importantly, neutralization of HER3 signaling with HER3 targeting monoclonal antibodies blocked LINC00052 mediated cancer cell proliferation in vitro and tumor growth in vivo, suggesting LINC00052 promoting cancer growth through HER3 signaling...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28004068/-up-regulation-of-erbb3-binding-protein-1-inhibits-the-growth-of-esophageal-carcinoma-cells
#4
Hao Jiang, Dong-Ping Liu, Dong Xie, Dong-Zhi Wei
The objective of this study was to investigate the role of ErbB3-binding protein 1 (Ebp1) in the growth of esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanism. Eca109 and KYSE150 cells were transfected with lentiviral vector carrying Ebp1 gene. The mRNA levels of Ebp1 in esophageal cancer tissues and paired adjacent normal tissues were examined by real-time PCR. The growth and viability of esophageal carcinoma cells were assessed using MTT and crystal violet assays, respectively. Clone-forming abilities of Eca109 and KYSE150 cells were analyzed by soft agar assay...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27998236/randomized-phase-ii-trial-of-seribantumab-in-combination-with-paclitaxel-in-patients-with-advanced-platinum-resistant-or-refractory-ovarian-cancer
#5
Joyce F Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria Del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R Wendel Naumann, Robert L Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27906435/down-regulation-of-microrna-143-is-associated-with-colorectal-cancer-progression
#6
J-W Bai, H-Z Xue, C Zhang
OBJECTIVE: Colorectal cancer (CRC) is one of the most prevalent carcinomas worldwide. Tumor metastasis and recurrence are leading causes of CRC-related deaths. Given the role of microRNA (miRNA) in CRC invasion and metastasis, we explored the association between miRNA-143 expression and clinicopathologic characteristics in CRC, as well as the effects of miRNA-143 on CRC cell invasion in vitro. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-143 in tissue specimens and cell lines...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27906180/mir-148a-3p-represses-proliferation-and-emt-by-establishing-regulatory-circuits-between-erbb3-akt2-c-myc-and-dnmt1-in-bladder-cancer
#7
Xiao Wang, Zhen Liang, Xin Xu, Jiangfeng Li, Yi Zhu, Shuai Meng, Shiqi Li, Song Wang, Bo Xie, Alin Ji, Ben Liu, Xiangyi Zheng, Liping Xie
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27845906/specific-micro-rna-expression-patterns-distinguish-the-basal-and-luminal-subtypes-of-muscle-invasive-bladder-cancer
#8
Andrea E Ochoa, Woonyoung Choi, Xiaoping Su, Arlene Siefker-Radtke, Bogdan Czerniak, Colin Dinney, David J McConkey
The roles of non-coding RNAs in controlling clinical and biological heterogeneity in bladder cancer remain unclear. We used TCGA's published dataset (n = 405 tumors) as a discovery cohort and created a new validation cohort to define the miRNA expression patterns in the basal and luminal molecular subtypes of muscle-invasive bladder cancer (MIBC). We identified 63 miRNAs by PAM, which optimally identified basal and luminal tumors. The targets of the top luminal miRNAs were activators of EMT (ZEB1, ZEB2) and basal subtype transcription (IL-6, EGFR, STAT3), whereas the targets of the top basal miRNAs were involved in adipogenesis pathways and luminal breast cancer (ERBB2, ERBB3)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27776045/microrna-148a-suppresses-the-proliferation-and-migration-of-pancreatic-cancer-cells-by-down-regulating-erbb3
#9
Hui Feng, Yalei Wang, Jiaojiao Su, Hongwei Liang, Chen-Yu Zhang, Xi Chen, Weiyan Yao
OBJECTIVES: ErbB3 (HER3) has been associated with pancreatic cancer progression, but little is known about its regulatory mechanisms. We investigated whether microRNAs (miRNAs) regulate levels of ErbB3 in pancreatic cancer cells. METHODS: We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Furthermore, the biological consequences of the targeting of ERBB3 by miR-148a were examined by cell proliferation and migration assays in vitro...
October 2016: Pancreas
https://www.readbyqxmd.com/read/27709558/dna-copy-number-alterations-gene-expression-changes-and-disease-free-survival-in-patients-with-colorectal-cancer-a-10-year-follow-up
#10
Elisabetta Bigagli, Carlotta De Filippo, Cinzia Castagnini, Simona Toti, Francesco Acquadro, Francesco Giudici, Marilena Fazi, Piero Dolara, Luca Messerini, Francesco Tonelli, Cristina Luceri
BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes...
December 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27648936/kitenin-functions-as-a-fine-regulator-of-erbb4-expression-level-in-colorectal-cancer-via-protection-of-erbb4-from-e3-ligase-nrdp1-mediated-degradation
#11
Eun Gene Sun, Kyung Hwa Lee, Yoo-Seung Ko, Hui Jeong Choi, Jung-In Yang, Jae Hyuk Lee, Ik Joo Chung, Yun-Woong Paek, Hangun Kim, Jeong A Bae, Kyung Keun Kim
Understanding the complex biological functions of E3-ubiquitin ligases may facilitate the development of mechanism-based anti-cancer drugs. We recently identified that the KITENIN/ErbB4-Dvl2-c-Jun axis works as a novel unconventional downstream signal of epidermal growth factor (EGF) in colorectal cancer (CRC) tissues. Here we addressed whether E3-ubiquitin ligases are required for operation of this axis. We found that Nrdp1, an E3-ligase for ErbB3/ErbB4, interacted with KITENIN (KAI1 C-terminal interacting tetraspanin) to form a functional KITENIN/ErbB4/Nrdp1 complex and is responsible for down-regulating Dvl2 within this complex...
September 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27633099/lapatinib-resistant-cancer-cells-possessing-epithelial-cancer-stem-cell-properties-develop-sensitivity-during-sphere-formation-by-activation-of-the-erbb-akt-cyclin%C3%A2-d2-pathway
#12
Yuichi Ohnishi, Hiroki Yasui, Kenji Kakudo, Masami Nozaki
Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer. In the present study, we examined the effects of lapatinib on growth of oral and prostate cancer cells. Oral squamous cell carcinoma (OSCC) cell lines HSC3, HSC4 and Ca9-22 were sensitive to the antiproliferative effects of lapatinib in anchorage-dependent culture, but the OSCC cell lines KB and SAS and the prostate cancer cell line DU145 were resistant to lapatinib...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27611608/ampulla-of-vater-carcinoma-sequencing-analysis-identifies-tp53-status-as-a-novel-independent-prognostic-factor-and-potentially-actionable-erbb-pi3k-and-wnt-pathways-gene-mutations
#13
Andrea Mafficini, Eliana Amato, Ivana Cataldo, Borislav C Rusev, Luca Bertoncello, Vincenzo Corbo, Michele Simbolo, Claudio Luchini, Matteo Fassan, Cinzia Cantù, Roberto Salvia, Giovanni Marchegiani, Giampaolo Tortora, Rita T Lawlor, Claudio Bassi, Aldo Scarpa
OBJECTIVE: To identify molecular prognostic factors and potentially actionable mutations in ampulla of Vater cancer (AVC). BACKGROUND: The largely variable outcomes of AVCs make clinical decisions difficult regarding the need of postsurgical therapy, which is based on morphological and immunohistochemical classification that do not adequately consider the varying degrees of heterogeneity present in many AVCs. No approved targeted therapies for AVC exist, but some show promising results requiring better molecular characterization to identify potential responders...
September 8, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27610130/prognostic-impact-of-mrna-expression-levels-of-her1-4-erbb1-4-in-patients-with-locally-advanced-rectal-cancer
#14
Melanie Kripp, Kirsten Merx, Ralph Markus Wirtz, Timo Gaiser, Sebastian Eidt, Juliana Schwaab, Stefan Post, Frederik Wenz, Andreas Hochhaus, Ralf-Dieter Hofheinz, Philipp Erben
Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC...
2016: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/27609096/paeoniflorin-potentiates-the-inhibitory-effects-of-erlotinib-in-pancreatic-cancer-cell-lines-by-reducing-erbb3-phosphorylation
#15
Jian Hao, Xue Yang, Xiu-Li Ding, Lei-Ming Guo, Cui-Hong Zhu, Wei Ji, Tong Zhou, Xiong-Zhi Wu
Blockade of the epidermal growth factor receptor (EGFR) by EGFR tyrosine kinase inhibitors is insufficient for effective anti-tumor activity because the reactivation of the ErbB3 signaling pathway significantly contributes to activating the consequent phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Combinatorial therapies including ErbB3 targeting may ameliorate tumor responses to anti-EGFR therapies. In the present study, we found that in BxPC-3 and L3.6pl cells, which highly expressed the ErbB3 receptor, significant reduction in cell viability, induction of apoptosis were observed when treated with a combination of erlotinib and PF compared to either agent alone...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27602491/erbb2-mutations-associated-with-solid-variant-of-high-grade-invasive-lobular-breast-carcinomas
#16
Gabrielle Deniziaut, Jean Christophe Tille, François-Clément Bidard, Sophie Vacher, Anne Schnitzler, Walid Chemlali, Laurence Trémoulet, Laetitia Fuhrmann, Paul Cottu, Roman Rouzier, Ivan Bièche, Anne Vincent-Salomon
ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8)...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27597943/the-under-appreciated-promiscuity-of-the-epidermal-growth-factor-receptor-family
#17
REVIEW
Sean P Kennedy, Jordan F Hastings, Jeremy Z R Han, David R Croucher
Each member of the epidermal growth factor receptor (EGFR) family plays a key role in normal development, homeostasis, and a variety of pathophysiological conditions, most notably in cancer. According to the prevailing dogma, these four receptor tyrosine kinases (RTKs; EGFR, ERBB2, ERBB3, and ERBB4) function exclusively through the formation of homodimers and heterodimers within the EGFR family. These combinatorial receptor interactions are known to generate increased interactome diversity and therefore influence signaling output, subcellular localization and function of the heterodimer...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27582551/novel-association-of-dj-1-with-her3-potentiates-her3-activation-and-signaling-in-cancer
#18
Shu Zhang, Seema Mukherjee, Xuejun Fan, Ahmad Salameh, Kalpana Mujoo, Zhao Huang, Leike Li, Georgina To'a Salazar, Ningyan Zhang, Zhiqiang An
HER3/ErbB3 has emerged as a new therapeutic target for cancer. Currently, more than a dozen anti-HER3 antibodies are in clinical trials for treatment of various cancers. However, limited understanding of the complex HER3 signaling in cancer and lack of established biomarkers have made it challenging to stratify cancer patients who can benefit from HER3 targeted therapies. In this study, we identified DJ-1/PARK7 (Parkinson Protein 7) as a novel interaction partner of HER3 and demonstrated the potential of DJ-1 as a biomarker for anti-HER3 cancer therapy...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27570763/effect-of-spatial-inhomogeneities-on-the-membrane-surface-on-receptor-dimerization-and-signal-initiation
#19
Romica Kerketta, Ádám M Halász, Mara P Steinkamp, Bridget S Wilson, Jeremy S Edwards
Important signal transduction pathways originate on the plasma membrane, where microdomains may transiently entrap diffusing receptors. This results in a non-random distribution of receptors even in the resting state, which can be visualized as "clusters" by high resolution imaging methods. Here, we explore how spatial in-homogeneities in the plasma membrane might influence the dimerization and phosphorylation status of ErbB2 and ErbB3, two receptor tyrosine kinases that preferentially heterodimerize and are often co-expressed in cancer...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27567286/rankl-signaling-and-erbb-receptors-in-breast-carcinogenesis
#20
Ilianna Zoi, Michalis V Karamouzis, Christos Adamopoulos, Athanasios G Papavassiliou
ErbB family members, ErbB1/EGFR/HER-1, ErbB2/HER-2, ErbB3/HER-3 and ErbB4/HER-4, have been implicated in breast cancer (BC) tumorigenicity. Recently, crucial roles for RANK/RANKL signaling in addition to key downstream factor NF-κB have been demonstrated in mammary tumorigenesis. Here, we present the hypothesis of a novel association between ErbB and RANK pathways in promoting BC. The proposed model alludes to the cross-talk that might occur between RANK and ErbB receptors. This interplay might regulate RANK signaling and consequently, modulate carcinogenesis, mainly in ErbB2 over-expressing BC cells...
October 2016: Trends in Molecular Medicine
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