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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/27906435/down-regulation-of-microrna-143-is-associated-with-colorectal-cancer-progression
#1
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
#2
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
#3
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
#4
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
#5
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...
October 5, 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
#6
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
#7
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...
September 7, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
August 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27570763/effect-of-spatial-inhomogeneities-on-the-membrane-surface-on-receptor-dimerization-and-signal-initiation
#14
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
#15
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
https://www.readbyqxmd.com/read/27551531/an-epithelial-marker-promoter-induction-screen-identifies-histone-deacetylase-inhibitors-to-restore-epithelial-differentiation-and-abolishes-anchorage-independence-growth-in-cancers
#16
H M Tang, K T Kuay, P F Koh, M Asad, T Z Tan, V Y Chung, S C Lee, J P Thiery, Ry-J Huang
Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27531070/feedback-control-of-erbb2-via-erk-mediated-phosphorylation-of-a-conserved-threonine-in-the-juxtamembrane-domain
#17
Yuki Kawasaki, Ayaka Sakimura, Chul Min Park, Rika Tomaru, Tomohiro Tanaka, Tatsuhiko Ozawa, Yue Zhou, Kaori Narita, Hiroyuki Kishi, Atsushi Muraguchi, Hiroaki Sakurai
Tyrosine kinase activity of the asymmetric EGFR homodimer is negatively regulated via ERK-mediated phosphorylation of Thr-669 in the juxtamembrane domain. In the present study, we investigated in human breast cancer cells whether a similar mechanism plays a role in the feedback regulation of the ErbB2/ErbB3 heterodimer, the most potent ErbB receptor dimer. Constitutive tyrosine phosphorylation of ErbB2 and ErbB3 was significantly decreased in phorbol ester- and growth factor-treated BT-474 and MDA-MB-453 cells...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27524912/two-gene-signature-improves-the-discriminatory-power-of-iaslc-ats-ers-classification-to-predict-the-survival-of-patients-with-early-stage-lung-adenocarcinoma
#18
Yifeng Sun, Likun Hou, Yu Yang, Huikang Xie, Yang Yang, Zhigang Li, Heng Zhao, Wen Gao, Bo Su
BACKGROUND: In this study, we investigated the contribution of a gene expression-based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR) to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27518467/microrna-148a-suppresses-the-proliferation-and-migration-of-pancreatic-cancer-cells-by-down-regulating-erbb3
#19
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/27474152/erbb2-overexpression-establishes-erbb3-dependent-hypersensitivity-of-breast-cancer-cells-to-withaferin-a
#20
Wenjun Liu, Annalise R Barnette, Samita Andreansky, Ralf Landgraf
The catalytically deficient ERBB3 strongly synergizes with the receptor tyrosine kinase ERBB2, and elevated levels represent an overall risk factor for unfavorable disease outcomes in breast cancer. Although itself not a target of pan-ERBB kinase inhibitors, it contributes to resistance in ERBB2-targeted treatment regiments. The steroidal lactone Withaferin A (WA) has established broad anticancer properties through several modes of action and was shown to be effective against triple-negative breast cancers at elevated concentrations...
July 29, 2016: Molecular Cancer Therapeutics
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