Epiregulin

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone...

Mutations of receptor tyrosine kinases (RTKs) are associated with the development of many cancers by modifying receptor signaling and contributing to drug resistance in clinical settings. We present enhanced bystander bioluminescence resonance energy transfer-based biosensors providing new insights into RTK biology and pharmacology critical for the development of more effective RTK-targeting drugs. Distinct SH2-specific effector biosensors allow for real-time and spatiotemporal monitoring of signal transduction pathways engaged upon RTK activation...

Epidermal growth factor (EGF) signaling regulates multiple cellular processes and plays an essential role in tumorigenesis. Epiregulin (EREG), a member of the EGF family, binds to the epidermal growth factor receptor (EGFR) and ErbB4, and it stimulates EGFR-related downstream pathways. Increasing evidence indicates that both the aberrant expression and oncogenic function of EREG play pivotal roles in tumor development in many human cancers, including non-small cell lung cancer (NSCLC). EREG overexpression is induced by activating mutations in the EGFR , KRAS , and BRAF and contributes to the aggressive phenotypes of NSCLC with oncogenic drivers...

BACKGROUND: Epiregulin is a molecule that plays a role in cell proliferation, tumor development, inflammation, and angiogenesis in malignant diseases. AIM: Our study aims to reveal, for the first time, the predictive value of this molecule in non-Hodgkin lymphoma (NHL) and its association with disease stage, cell type, and extranodal involvement. METHODS: The study is an observational case-control trial involving 60 newly diagnosed NHL patients and 60 healthy individuals (control group) between 18 and 75 years old...

Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes are often studied separately. To functionally map how cell-intrinsic and cell-extrinsic cues co-regulate cell fate, we performed a systematic single-cell analysis of 1,107 colonic organoid cultures regulated by (1) colorectal cancer (CRC) oncogenic mutations, (2) microenvironmental fibroblasts and macrophages, (3) stromal ligands, and (4) signaling inhibitors. Multiplexed single-cell analysis revealed a stepwise epithelial differentiation phenoscape dictated by combinations of oncogenes and stromal ligands, spanning from fibroblast-induced Clusterin (CLU)+ revival colonic stem cells (revCSCs) to oncogene-driven LRIG1+ hyper-proliferative CSCs (proCSCs)...

Although tamoxifen (TAM) is widely used in patients with estrogen receptor-positive breast cancer, the development of tamoxifen resistance is common. The previous finding suggests that the development of tamoxifen resistance is driven by epiregulin or hypoxia-inducible factor-1α-dependent glycolysis activation. Nonetheless, the mechanisms responsible for cancer cell survival and growth in a lactic acid-rich environment remain elusive. We found that the growth and survival of tamoxifen-resistant MCF-7 cells (TAMR-MCF-7) depend on glycolysis rather than oxidative phosphorylation...

Signaling bias is the ability of a receptor to differentially activate downstream signaling pathways in response to different ligands. Bias investigations have been hindered by inconsistent results in different cellular contexts. Here we introduce a methodology to identify and quantify bias in signal transduction across the plasma membrane without contributions from feedback loops and system bias. We apply the methodology to quantify phosphorylation efficiencies and determine absolute bias coefficients. We show that the signaling of epidermal growth factor receptor (EGFR) to EGF and TGFα is biased towards Y1068 and against Y1173 phosphorylation, but has no bias for epiregulin...

The tumor microenvironment (TME) consists of cancer cells surrounded by stromal components including tumor vessels. Transforming growth factor-β (TGF-β) promotes tumor progression by inducing epithelial-mesenchymal transition (EMT) in cancer cells and stimulating tumor angiogenesis in the tumor stroma. We previously developed an Fc chimeric TGF-β receptor containing both TGF-β type I (TβRI) and type II (TβRII) receptors (TβRI-TβRII-Fc), which trapped all TGF-β isoforms and suppressed tumor growth...

Cervical cancer (CC) is the fourth most gynecological malignancy in the world. The identification of predictive markers can provide a basis for personalized treatment and prognostic evaluation. Our aim was to identify a new predictive marker of epiregulin (EREG) gene and explore its functional characteristics of CC and other cancer types. Differentially highly expressed genes were obtained from Gene Expression Omnibus (GEO) databases. Key genes can be verified by the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) data, and the functions of these genes were investigated through gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis...

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Although dermatology offers advanced interventions, molecular mechanisms in skin aging remain limited. Competing endogenous RNAs (ceRNAs), a subset of coding or non-coding RNAs, regulate gene expression through miRNA competition. Several ceRNA networks investigated up to now offer insights into skin aging and wound healing. In skin aging, RP11-670E13.6-miR-663a-CDK4/CD6 delays senescence induced by UVB radiation. Meg3-miR-93-5p-epiregulin contributes to UVB-induced inflammatory skin damage...

The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D...

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield...

ADAM17, a prominent member of the "Disintegrin and Metalloproteinase" (ADAM) family, controls vital cellular functions through the cleavage of transmembrane substrates, including epidermal growth factor receptor (EGFR) ligands such as transforming growth factor (TGF)-alpha and Epiregulin (EREG). Several ADAM17 substrates are relevant to oncogenesis and tumor growth. We have presented evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. The scramblase Xkr8 is instrumental for calcium-independent exposure of PS in apoptotic cells...

BACKGROUND: In experimental studies, intravitreally applied antibodies against epidermal growth factor (EGF), EGF family members (amphiregulin, neuregulin-1, betacellulin, epigen, epiregulin) and against the EGF receptor (EGFR) were associated with a reduction in lens-induced axial elongation and decrease in physiological eye elongation in guinea pigs and in non-human primates. Here, we investigated the intraocular tolerability and safety of a fully human monoclonal IgG2-antibody against EGFR, already in clinical use in oncology, as a potential future therapeutic approach for axial elongation in adult eyes with pathological myopia...

UNLABELLED: The biophysical properties of ligand binding heavily influence the ability of receptors to specify cell fates. Understanding the rules by which ligand binding kinetics impact cell phenotype is challenging, however, because of the coupled information transfers that occur from receptors to downstream signaling effectors and from effectors to phenotypes. Here, we address that issue by developing an integrated mechanistic and data-driven computational modeling platform to predict cell responses to different ligands for the epidermal growth factor receptor (EGFR)...

PURPOSE: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG immunohistochemistry (IHC) was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. EXPERIMENTAL DESIGN: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible...

The prognosis of gallbladder cancer (GBC) remains poor, and a better understanding of GBC molecular mechanisms is important. Genome sequencing of human GBC has demonstrated that loss-of-function mutations of E74-like ETS transcription factor 3 (ELF3) are frequently observed, with ELF3 considered to be a tumour suppressor in GBC. To clarify the underlying molecular mechanisms by which ELF3 suppresses GBC development, we performed in vivo analysis using a combination of autochthonous and allograft mouse models...

MicroRNA-1179 (miRNA-1179) is an extensively studied tumor suppressor. however, the significance of miR-1179 in multiple myeloma has not been investigated previously. So, there is a need for research to find out about the significance of miR-1179 in multiple myeloma. However, current investigations have examined the significance of miRNA-1179 in multiple myeloma for the first time by targeting epiregulin (EREG). In this study, 26 multiple myeloma specimens and 16 healthy donor specimens were examined. Multiple myeloma cell lines (U266, RPMI-8226, KMS-11, JJN-3, and IM-9) were used...

BACKGROUND AND AIMS: Lactylation, a recently identified post-translational modification (PTM), plays a central role in the regulation of multiple physiological and pathological processes. Exercise is known to provide protection against cardiovascular disease. However, whether exercise-generated lactate changes lactylation and is involved in the exercise-induced attenuation of atherosclerotic cardiovascular disease (ASCVD) remains unclear. The purpose of this study was to investigate the effects and mechanisms of exercise-induced lactylation on ASCVD...

The IL-6 amplifier, which describes the simultaneous activation of STAT3 and NF-kB, in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-kB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NFkB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-kB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and CCL2, phenotypes consistent with in vitro experiments...