2,087 results match your criteria erbb signalling

Curcumin and cancer biology: Focusing regulatory effects in different signalling pathways.

Phytother Res 2021 Apr 9. Epub 2021 Apr 9.

Poona college of pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, India.

Cancer is the second-leading cause of death worldwide. Till date, many such effective treatments are available, for example chemotherapy, surgery, and radiation therapy, but there are severe associated side effects, such as increased infection risk, constipation, hair loss, anaemia, among others. Thus, the need for effective therapeutic strategies and screening methodology arises. Read More

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Novel Resistance Mechanisms to Osimertinib Analysed by Whole-Exome Sequencing in Non-Small Cell Lung Cancer.

Cancer Manag Res 2021 25;13:2025-2032. Epub 2021 Feb 25.

Respiratory Department of Chinese PLA General Hospital, Beijing, People's Republic of China.

Purpose: Molecular-based targeted therapy has improved life expectancy for advanced non-small cell lung cancer (NSCLC). However, it does not have to be inevitable that patients receiving third-generation EGFR-TKIs become drug resistant. EGFR C797S and MET amplification are common mechanisms of osimertinib. Read More

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February 2021

Signalling pathways and mechanistic cues highlighted by transcriptomic analysis of primordial, primary, and secondary ovarian follicles in domestic cat.

Sci Rep 2021 Jan 29;11(1):2683. Epub 2021 Jan 29.

Reproduction Biology Department, Leibniz Institute for Zoo and Wildlife Research, Alfred-Kowalke-Straße 17, 10315, Berlin, Germany.

In vitro growth (IVG) of dormant primordial ovarian follicles aims to produce mature competent oocytes for assisted reproduction. Success is dependent on optimal in vitro conditions complemented with an understanding of oocyte and ovarian follicle development in vivo. Complete IVG has not been achieved in any other mammalian species besides mice. Read More

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January 2021

Antitumour immunity regulated by aberrant ERBB family signalling.

Nat Rev Cancer 2021 03 18;21(3):181-197. Epub 2021 Jan 18.

Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. Molecular-targeted agents against these signalling pathways exhibit robust clinical efficacy, but patients inevitably experience acquired resistance to these molecular-targeted therapies. Although cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have shown durable antitumour response in a subset of the treated patients in multiple cancer types, clinical efficacy is limited in cancers harbouring activating gene alterations of ERBB family members. Read More

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Structure-Activity Relationship (SAR) Study of Spautin-1 to Entail the Discovery of Novel NEK4 Inhibitors.

Int J Mol Sci 2021 Jan 10;22(2). Epub 2021 Jan 10.

Research Group of Organic Chemistry, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.

Lung cancer is one of the most frequently diagnosed cancers accounting for the highest number of cancer-related deaths in the world. Despite significant progress including targeted therapies and immunotherapy, the treatment of advanced lung cancer remains challenging. Targeted therapies are highly efficacious at prolonging life, but not curative. Read More

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January 2021

Increase of the Intracellular Zinc Concentration Leads to an Activation and Internalisation of the Epidermal Growth Factor Receptor in A549 Cells.

Int J Mol Sci 2020 Dec 30;22(1). Epub 2020 Dec 30.

Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, Germany.

(1) Background: Zinc is suggested to play a major role in epidermal growth factor (EGF)-induced cell regeneration and proliferation. To deepen the knowledge on the underlying mechanisms zinc's effects on the epidermal growth factor receptor (EGFR) activation and its endocytosis was investigated in the alveolar carcinoma cell line A549. (2) Methods: An increase of intracellular zinc was generated by adding zinc extracellularly compared to the intracellular release of zinc from zinc-binding proteins by stimulation with a nitric oxide donor. Read More

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December 2020

The role of the MAD2-TLR4-MyD88 axis in paclitaxel resistance in ovarian cancer.

PLoS One 2020 28;15(12):e0243715. Epub 2020 Dec 28.

Department of Histopathology, Trinity College Dublin, Dublin, Ireland.

Despite the use of front-line anticancer drugs such as paclitaxel for ovarian cancer treatment, mortality rates have remained almost unchanged for the past three decades and the majority of patients will develop recurrent chemoresistant disease which remains largely untreatable. Overcoming chemoresistance or preventing its onset in the first instance remains one of the major challenges for ovarian cancer research. In this study, we demonstrate a key link between senescence and inflammation and how this complex network involving the biomarkers MAD2, TLR4 and MyD88 drives paclitaxel resistance in ovarian cancer. Read More

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February 2021

miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis.

Reprod Biomed Online 2021 Mar 22;42(3):579-588. Epub 2020 Oct 22.

Division of Human Reproduction, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto - USP, São Paulo, Brazil; National Institute of Hormones and Women's Health - CNPq, Porto Alegre, Brazil. Electronic address:

Research Question: Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis?

Design: In this prospective case-control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal-Wallis test, followed by Benjamini-Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. Read More

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Coiled-coil domain containing 50-V2 protein positively regulates neurite outgrowth.

Sci Rep 2020 12 4;10(1):21295. Epub 2020 Dec 4.

Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.

The coiled-coil domain containing 50 (CCDC50) protein is a phosphotyrosine-dependent signalling protein stimulated by epidermal growth factor. It is highly expressed in neuronal cells in the central nervous system; however, the roles of CCDC50 in neuronal development are largely unknown. In this study, we showed that the depletion of CCDC50-V2 impeded the neuronal development process, including arbor formation, spine density development, and axonal outgrowth, in primary neurons. Read More

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December 2020

Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling.

Sci Rep 2020 12 3;10(1):21128. Epub 2020 Dec 3.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland.

Lung malignancies comprise lethal and aggressive tumours that remain the leading cancer-related death cause worldwide. Regarding histological classification, lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) account for the majority of cases. Surgical resection and various combinations of chemo- and radiation therapies are the golden standards in the treatment of lung cancers, although the five-year survival rate remains very poor. Read More

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December 2020

SNX29, a new susceptibility gene shared with major mental disorders in Han Chinese population.

World J Biol Psychiatry 2020 Dec 8:1-9. Epub 2020 Dec 8.

Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

Objectives: Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether gene played a significant role in these psychiatric disorders in the Han Chinese population. Read More

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December 2020

Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4.

Nat Cell Biol 2020 11 2;22(11):1357-1370. Epub 2020 Nov 2.

School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

The canonical model of agonist-stimulated phosphatidylinositol-3-OH kinase (PI3K)-Akt signalling proposes that PI3K is activated at the plasma membrane, where receptors are activated and phosphatidylinositol-4,5-bisphosphate is concentrated. Here we show that phosphatidylinositol-3,4,5-trisphosphate generation and activated Akt are instead largely confined to intracellular membranes upon receptor tyrosine kinase activation. Microtubule-associated protein 4 (MAP4) interacts with and controls localization of membrane vesicle-associated PI3Kα to microtubules. Read More

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November 2020

ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration.

Nat Cell Biol 2020 11 12;22(11):1346-1356. Epub 2020 Oct 12.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Cardiomyocyte loss after injury results in adverse remodelling and fibrosis, inevitably leading to heart failure. The ERBB2-Neuregulin and Hippo-YAP signalling pathways are key mediators of heart regeneration, yet the crosstalk between them is unclear. We demonstrate that transient overexpression of activated ERBB2 in cardiomyocytes (OE CMs) promotes cardiac regeneration in a heart failure model. Read More

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November 2020

Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma.

J Hematol Oncol 2020 10 2;13(1):130. Epub 2020 Oct 2.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, NO.270 DongAn Road, Shanghai, 200032, China.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. Read More

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October 2020

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways.

Molecules 2020 Sep 18;25(18). Epub 2020 Sep 18.

Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF"-University of Palermo, Viale delle Scienze - Ed. 17, 90128 Palermo, Italy.

The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. Read More

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September 2020

Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights.

Sci Rep 2020 09 7;10(1):14706. Epub 2020 Sep 7.

Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.

Prodigiosin, a secondary metabolite red pigment produced by Serratia marcescens, has an interesting apoptotic efficacy against cancer cell lines with low or no toxicity on normal cells. HSP90α is known as a crucial and multimodal target in the treatment of TNBC. Our research attempts to assess the therapeutic potential of prodigiosin/PU-H71 combination on MDA-MB-231 cell line. Read More

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September 2020

16-Hydroxycleroda-3,13-dien-15,16-olide Induces Apoptosis in Human Bladder Cancer Cells through Cell Cycle Arrest, Mitochondria ROS Overproduction, and Inactivation of EGFR-Related Signalling Pathways.

Molecules 2020 Aug 30;25(17). Epub 2020 Aug 30.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.

A clerodane diterpene compound 16-hydroxycleroda-3,13-dien-15,16-olide (CD) is considered a therapeutic agent with pharmacological activities. The present study investigated the mechanisms of CD-induced apoptosis in T24 human bladder cancer cells. CD inhibited cell proliferation in a concentration and time-dependent manner. Read More

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A small molecule inhibitor of HER3: a proof-of-concept study.

Biochem J 2020 09;477(17):3329-3347

Protein Phosphorylation Laboratory, The Francis Crick Institute, London, U.K.

Despite being catalytically defective, pseudokinases are typically essential players of cellular signalling, acting as allosteric regulators of their active counterparts. Deregulation of a growing number of pseudokinases has been linked to human diseases, making pseudokinases therapeutic targets of interest. Pseudokinases can be dynamic, adopting specific conformations critical for their allosteric function. Read More

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September 2020

Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy.

Cell Death Dis 2020 08 14;11(8):631. Epub 2020 Aug 14.

Paris-Saclay Institute of Neuroscience, CERTO-Retina France, CNRS, Université Paris-Saclay, Orsay, 91405, France.

Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. Read More

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GRB7 is an oncogenic driver and potential therapeutic target in oesophageal adenocarcinoma.

J Pathol 2020 11 15;252(3):317-329. Epub 2020 Sep 15.

Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Efficacious therapeutic approaches are urgently needed to improve outcomes in patients with oesophageal adenocarcinoma (OAC). However, oncogenic drivers amenable to targeted therapy are limited and their functional characterisation is essential. Among few targeted therapies available, anti-human epidermal growth factor receptor 2 (HER2) therapy showed only modest benefit for patients with OAC. Read More

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November 2020

The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma.

Cell Death Dis 2020 07 30;11(7):597. Epub 2020 Jul 30.

Medical School, Kunming University of Science and Technology, Kunming, 650500, China.

Oesophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy. Although many molecular alterations have been observed in ESCC, the mechanisms underlying the development and progression of this disease remain unclear. In the present study, miR-1224-5p was identified to be downregulated in ESCC tissues compared to normal tissues, and its low expression was correlated with shorter survival time in patients. Read More

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Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology.

Sci Rep 2020 07 29;10(1):12745. Epub 2020 Jul 29.

Beijing University of Chinese Medicine, Beijing, 100102, China.

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). Read More

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RhoA/C inhibits proliferation by inducing the synthesis of GPRC5A.

Sci Rep 2020 07 27;10(1):12532. Epub 2020 Jul 27.

Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University of Freiburg, Albert-Str. 25, 79104, Freiburg, Germany.

Rho GTPases are important regulators of many cellular functions like cell migration, adhesion and polarity. The molecular switches are often dysregulated in cancer. We detected Rho-dependent upregulation of the orphan seven-transmembrane receptor G-protein-coupled receptor family C group 5 member A (GPRC5A). Read More

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Progesterone receptor membrane component 1 promotes the growth of breast cancers by altering the phosphoproteome and augmenting EGFR/PI3K/AKT signalling.

Br J Cancer 2020 10 24;123(8):1326-1335. Epub 2020 Jul 24.

Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, 79905, USA.

Background: Increased expression of the progesterone receptor membrane component 1 (PGRMC1) has been linked to multiple cancers, including breast cancer. Despite being a regulatory receptor and a potential therapeutic target, the oncogenic potential of PGRMC1 has not been studied.

Methods: The impact of PGRMC1 on breast cancer growth and progression was studied following chemical inhibition and alteration of PGRMC1 expression, and evaluated by using online-based gene expression datasets of human breast cancer tissue. Read More

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October 2020

ADAM-Mediated Signalling Pathways in Gastrointestinal Cancer Formation.

Int J Mol Sci 2020 Jul 20;21(14). Epub 2020 Jul 20.

Institute of Biochemistry, Christian-Albrechts-University, 24118 Kiel, Germany.

Tumour growth is not solely driven by tumour cell-intrinsic mechanisms, but also depends on paracrine signals provided by the tumour micro-environment. These signals comprise cytokines and growth factors that are synthesized as trans-membrane proteins and need to be liberated by limited proteolysis also termed ectodomain shedding. Members of the family of A disintegrin and metalloproteases (ADAM) are major mediators of ectodomain shedding and therefore initiators of paracrine signal transduction. Read More

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NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism.

Nat Metab 2020 04 20;2(4):318-334. Epub 2020 Apr 20.

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.

The survival and recurrence of dormant tumour cells following therapy is a leading cause of death in cancer patients. The metabolic properties of these cells are likely distinct from those of rapidly growing tumours. Here we show that Her2 down-regulation in breast cancer cells promotes changes in cellular metabolism, culminating in oxidative stress and compensatory upregulation of the antioxidant transcription factor, NRF2. Read More

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Disease-related cellular protein networks differentially affected under different EGFR mutations in lung adenocarcinoma.

Sci Rep 2020 07 2;10(1):10881. Epub 2020 Jul 2.

Department of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan.

It is unclear how epidermal growth factor receptor EGFR major driver mutations (L858R or Ex19del) affect downstream molecular networks and pathways. This study aimed to provide information on the influences of these mutations. The study assessed 36 protein expression profiles of lung adenocarcinoma (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Read More

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EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.

Br J Cancer 2020 09 30;123(6):942-954. Epub 2020 Jun 30.

Department of Dermatology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.

Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. Read More

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September 2020

YES1 amplification confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive cancer.

Br J Cancer 2020 09 23;123(6):1000-1011. Epub 2020 Jun 23.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.

Background: Trastuzumab-emtansine (T-DM1), one of the most potent HER2-targeted drugs, shows impressive efficacy in patients with HER2-positive breast cancers. However, resistance inevitably occurs and becomes a critical clinical problem.

Methods: We modelled the development of acquired resistance by exposing HER2-positive cells to escalating concentrations of T-DM1. Read More

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September 2020

Gremlin-1 augments the oestrogen-related receptor α signalling through EGFR activation: implications for the progression of breast cancer.

Br J Cancer 2020 09 23;123(6):988-999. Epub 2020 Jun 23.

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.

Background: Gremlin-1 (GREM1), one of the bone morphogenetic protein antagonists, is involved in organogenesis, tissue differentiation and kidney development. However, the role of GREM1 in cancer progression and its underlying mechanisms remain poorly understood.

Methods: The role of GREM1 in breast cancer progression was assessed by measuring cell viability, colony formation, 3D tumour spheroid formation/invasion and xenograft tumour formation. Read More

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September 2020