China
Africa
Explore chapters and articles related to this topic
The Role of Growth Factor Signaling in the Development and Treatment of Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Rita D. Shelby, Terrence M. Rager, Barrett P. Cromeens, Gail E. Besner
Heparin-binding EGF-like growth factor (HB-EGF) is a glycoprotein first identified in the conditioned medium of cultured human macrophages (44) and a member of the EGF family (45). The HB-EGF gene is an immediate early gene induced by hypoxic and oxidative stress in response to tissue damage and resultant wound healing and tissue regeneration (46–51). It has potent mitogenic, chemoattractant, and migration-inducing effects that are mediated through activation of ErbB-1 and ErbB-4 receptors (52, 53). In addition, HB-EGF binds strongly to heparin (44). HB-EGF is found in both AF and BM, ensuring continuous exposure of fetal and newborn intestine to endogenous levels of the growth factor (54). Endogenous HB-EGF is expressed in many cell types, including intestinal epithelial cells (55, 56).
Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
The loss of heterozygosity, often with isochromosome 17q, is a characteristic change. The dysregulation of ErbB2 and ErbB4 was identified in the early stages of molecular profiling.140,141
Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Anthony J. Demetris, J.G. Lunz, Vladimir Subbotin, Tong Wu, Isao Nozaki, Sarah Contrucci, Xia Yin
The ErbB receptor family of type I receptor tyrosine kinases has four members: EGFR (or ErbB1/Her1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. All family members have in common an extracellular ligand-binding domain, a single transmembrane region and a cytoplasmic protein tyrosine kinase domain.98,99 Ligand binding leads to receptor aggregation in coated pits and vesicles, which appears to be essential for signal propagation. Receptor aggregation also forms the basis for homo- and heterodimeric interactions within the ErbB family of proteins.98,99 Trans-phosphorylation of tyrosine residues in multimeric complexes results in tyrosine phosphorylation of a number of intracellular substrates including PLC-(gamma), the GTPase-activating protein (GAP) of the ras proto-oncogene and lipocortin I (Fig. 3).98,99 Many of these proteins interact with the activated EGFR through Src homology 2 (SH2) domains, sequences of about 100 amino acids that specifically recognize phosphotyrosines. Readers interested in more detail about the EGF signaling pathways in general and liver reactions, in specific, are referred elsewhere.98,99
The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells in vitro
Published in International Journal of Neuroscience, 2021
Xizhong Yang, Cuijie Ji, Xinyue Liu, Chaoqun Zheng, Yanxin Zhang, Ruowu Shen, Zangong Zhou
To reconcile these differences in the reported repertoire of ErbB receptor expression in SC, Schwann-like cells from different stages were assayed by reverse transcriptase (RT)-PCR to ErbB receptors. The expression quantity alteration of ErbB receptors indicated that ErbB2 and its ligand neuregulin 1 are necessary to change the cell phenotype. ErbB3 began to take effect after being treated with inducing factors like heregulin and bFGF. However, ErbB4 cannot be detected whether ErbB2 signaling is being blocked or not, which is similar to findings in the peripheral nerve system. Pharmacological blockade of ErbB2 potently reduced SC proliferation and induced apoptosis. Immunofluorescence staining revealed that the special marker protein of SC decreased its expression due to the suppression of ErbB2 signaling. To address the role of different phenotypes of ErbB in differentiation and to investigate how these phenotypes interact, we employed several assays, in which we pharmacologically uncoupled ErbB signaling from SC differentiation. Our analysis demonstrates that ErbB2 levels during differentiation increased to accelerate the transformation from BMSC to SC and that treatment with inducing factors can induce ErbB3 up-regulation and form a heterodimer with ErbB2 to active downstream pathways like Grb2, Shc, Sos, PLCγ, PI3K, Src and their receptors and activate cell downstream signaling cascades (such as PI3K/Akt, Ras/Erk1/2, PLCγ). The previous study points out that PI3K/Akt pathway is closely related to proliferation and viability, which play an important role in SCs [18].
miR-93-5p knockdown repressed hepatocellular carcinoma progression via increasing ERBB4 and TETs-dependent DNA demethylation
Published in Autoimmunity, 2021
Yuqiang Li, Bin Wu, Rongli Sun, Mingzhou Zhao, Nan Li
DNA methylation is an important modification for gene repression [10], and it opens the access to develop novel targets for HCC treatment [11]. Moreover, miRNAs can regulate DNA methylation via controlling DNA methyltransferases activity [12]. The ten-eleven translocation methyl-cytosine dioxygenases (TETs) control DNA demethylation, which have crucial function in cancers, including HCC [13,14]. In addition, miRNAs can regulate the stability of TETs (TET1, TET2 and TET3) to affect the related gene expression in cancers [15–17]. Erb-B2 receptor tyrosine kinase 4 (ERBB4) has a tumour inhibiting property in cancers [18]. A previous study reported ERBB4 could repress HCC development [19]. In our preliminary experiments, we found that ERBB4 was a hypermethylated gene in HCC cells. The bioinformatics analysis used starBase (http://starbase.sysu.edu.cn/) to predict that miR-93-5p might target ERBB4 and TETs. Hence, we hypothesised that miR-93-5p might regulate ERBB4 expression via direct target and TETs-dependent DNA methylation, which has not been reported.
New insights into ErbB3 function and therapeutic targeting in cancer
Published in Expert Review of Anticancer Therapy, 2020
Umbreen Hafeez, Adam C Parslow, Hui K Gan, Andrew M Scott
Despite the range of new anti-cancer drugs in the market, there were 9.6 million deaths from cancer globally in 2018, approximately one in six deaths were due to cancer [1]. Researchers are trying to discover novel strategies to target various survival signaling pathways that play an essential role in the development and progression of cancer. One group of receptors that have proven to be excellent targets for cancer therapy is the ErbB family. The human ErbB family comprises of four receptor tyrosine kinases that reside on the cell surface: ErbB1 (EGFR, HER1); ErbB2 (HER2, Neu); ErbB3 (HER3); and ErbB4 (HER4). ErbB family members play an essential role in development and oncogenesis [2]. Targeting the first two of these family members, EGFR and ErbB2, have resulted in improved survival in multiple cancers, including cancers of the breast, colon, stomach, head and neck, and lung [3–5]. Given the success in targeting EGFR and ErbB2, there is a significant interest in targeting ErbB3 and ErbB4. Similar strategies could be used to target the latter two since there are substantial structural similarities across all four family members. Here we focus on ErbB3 as a target in cancer, with overexpression, amplification, and mutations identified in a variety of cancer types. We give a brief outline of various strategies to target ErbB3 and its partners and summarize critical results from clinical trials involving ErbB3 directed antibodies in a variety of tumor types.