Molecular Drivers in Lung Adenocarcinoma: Therapeutic Implications
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
HER-2 is a member of the Human epidermal growth factor receptor (HER) family of transmembrane receptor tyrosine kinases. Other members of this family include HER1 (epidermal growth factor receptor [EGFR]), HER3 (erbB3), and HER4 (erbB4). HER2 is constitutively active and has no ligand. Overexpression, gene amplification or mutation of HER-2 affects the downstream PI3K-Akt and MAPK pathways, leading to the disruption of the regulation of cell-cycle progression and apoptosis [80, 81]. Approximately 2-4% of NSCLC have HER2 mutations, which seem to be mutually exclusive from EGFR/KRAS/ALK-mutations. HER-2 gene amplification and HER-2 over expression are more prevalent (20% and 35% of NSCLC cases) [82]. HER-2 overexpression [by immunohistochemistry (IHC)] was found to be a marker for poor prognosis in NSCLC (HR 1.48; 95% CI: 1.22–1.80) in a meta-analysis of 6135 patients [83].
Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
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
Molecular Diagnostics of Pulmonary Neoplasms
Philip T. Cagle, Timothy C. Allen, Mary Beth Beasley in Diagnostic Pulmonary Pathology, 2008
The epidermal growth factor receptor (EGFR, HER-1/ErbB1) is a member of the ErbB family of tyrosine kinase receptors (TK), which includes HER-1/ErbB1, HER-2/neu/ErbB2, HER-3/ErbB3, and HER-4/ErbB4. Upon ligand binding and receptor homodimerization or heterodimerization and activation, activated EGFR signals downstream to the PI3K/AKT and RAS/RAF/MAPK pathways. These intracellular signaling pathways regulate key processes such as apoptosis, proliferation, and angiogenesis. EGFR is expressed in a large proportion of epithelial tumors and its role in lung cancer has been known for decades.
Epidermal growth factor receptor based active targeting: a paradigm shift towards advance tumor therapy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Md. Habban Akhter, Nv Sateesh Madhav, Javed Ahmad
ErbB2 is the second member of EGF receptor. The ligand of ErbB2 is not yet discovered for binding with this receptor homodimer. On the contrary, this forms heterodimers with other family members and such dimers can bind with growth factors receptor. It is over-expressed in colon, lungs, cervix, breast and pancreatic cancers. ErbB3 lack tyrosine kinase domain due to homogeneity with other members of the family. Rather, it forms heterodimer with other family members and is also seen to assist in cascades of signaling pathway. Breast cancer, colon, prostrate and stomach has shown dominance for this receptor. ErbB4 is last family member of EGF receptor comprises 75% in transmembrane domain, 70% in intracellular tyrosine kinase domain (276 residues) and 20% in regulated carboxyl terminal or cytoplasmic tail. It is over-expressed in ovary and breast cancer. The ErbB proteins are homologous to the avian viral oncogene v-ErbB.
In vitro study of the effects of DC electric fields on cell activities and gene expression in human choriocarcinoma cells
Published in Electromagnetic Biology and Medicine, 2021
Jinxin Chen, Linbo Guan, Ping Fan, Xinghui Liu, Rui Liu, Yu Liu, Huai Bai
ErbB belongs to the human epidermal growth factor receptor (HER) family of transmembrane tyrosine kinases, including ErbB1(EGFR), ErbB2, ErbB3, and ErbB4 (Sirica 2008). Upon ligand binding, ErbB homodimers or heterodimers are activated by autophosphorylation and then combine with some intermediate proteins, which elicit several downstream cascades and lead to important biological effects, including cell movement, proliferation, adhesion, and differentiation (Linggi and Carpenter 2006; Sirica 2008). Our results showed that the expression of EGFR, ErbB4, Crk (CrkL), CDKN1A (P21), and JUN genes was upregulated in the ErbB signaling pathway in choriocarcinoma cells stimulated by DC EF. Several studies have shown that the overexpression or overactivity of EGFR is associated with enhanced migration or proliferation of several types of cells, including keratinocytes and myofibroblasts (Andl et al. 2003; Zuo et al. 2018).
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
ERBB4 could induce cell apoptosis in breast cancer [33]. Additionally, Ni et al. reported ERBB4 could act as a suppressor in colitis-associated cancer [34]. These suggested ERBB4 might play a tumour-suppressive role in some cancers. A previous study suggested ERBB4 could exhibit a protective role in hepatitis B viral infection [35]. Due to the hepatitis B viral infection as a main risk factor for HCC, we hypothesized ERBB4 might also have an anti-HCC activity. Liu et al. reported low expression of ERBB4 was related to lower survival of patients, and ERBB4 acted as a suppressor in HCC [19]. Consistent with this report, our study also found the anti-HCC function of ERBB4. Moreover, we found ERBB4 could be directly targeted via miR-93-5p and reversed the influence of miR-93-5p on HCC cell progression. These results indicated miR-93-5p directly targeted ERBB4 to control HCC progression.
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