scholarly journals Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joel Zindel ◽  
Jonas Mittner ◽  
Julia Bayer ◽  
Simon L. April-Monn ◽  
Andreas Kohler ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adhesion Formation ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Egfr Signaling ◽  
Peritoneal Adhesions ◽  
Egfr Inhibition ◽  
Egfr Expression ◽  
Epidermal Growth

AbstractAbdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arise from the mesothelium. This transformation is driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor, are sufficient to induce these changes. Correspondingly, EGFR inhibition leads to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients are enriched in EGFR positive cells of mesothelial origin and human mesothelium shows an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery.

Recent Advances on Epidermal Growth Factor Receptor as a Molecular Target for Breast Cancer Therapeutics

2020 ◽  
Vol 21 ◽  
Author(s):  
Swathi R. Shetty ◽  
Ragini Yeeravalli ◽  
Tanya Bera ◽  
Amitava Das
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Type I ◽  
Egfr Inhibition ◽  
Epidermal Growth

: Epidermal growth factor receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that trigger tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Further, the mechanisms of action of potential molecules at various stages of drug development as well as clinically approved drugs for breast cancer treatment are illustrated.

scholarly journals CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jun Yu ◽  
Qianwen Zheng ◽  
Zhiran Li ◽  
Yunhao Wu ◽  
Yangbo Fu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Stem Cell ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Gene Set Enrichment Analysis ◽  
Germline Stem Cell ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Epidermal Growth

AbstractSpermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.

scholarly journals Epidermal growth factor receptor protein expression in lung cancer and survival analysis

2018 ◽  
Vol 5 (3) ◽  
pp. 550
Author(s):  
Shivalingaswamy Salimath ◽  
Jayaraj B. S. ◽  
Mahesh P. A. ◽  
M. D. Majeed Pasha ◽  
Lokesh K. S. ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Multivariate Analysis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Nsclc Patients

Background: Epidermal Growth Factor Receptor (EGFR) is one of the important molecules involved in lung cancer initiation and progression. Studies on over expression of EGFR and its survival in relation with Non-small cell lung cancer (NSCLC) patients have yielded controversial results. Prevalence of EGFR expression in NSCLC patients and 6-month survival in south Indian population is unknown.Methods: We carried out a prospective study in tertiary hospital. Diagnosed patients with NSCLC were included in the study and were interviewed with questionnaire containing demography and investigations like Chest X-ray, CT thorax, Bronchoscopy were recorded. EGFR expression analysis was done for all patients and were followed up monthly for 6 months and details of survival and treatment were collected. Cox regression analysis was used to assess their survival.Results: 50 patients with NSCLC were included. Forty-four (88%) were men, median age of study group was 65 years. Twenty-seven patients (54%) had Adenocarcinoma, 14 patients (28%) had Squamous cell carcinoma, 7 patients (14%) had poorly differentiated carcinoma and 2 patients (4%) had large cell carcinoma. Thirty-four (68%) samples were positive for EGFR expression. On multivariate analysis we found patients who took chemotherapy and with good performance status (Karnofsky score >65 and Eastern Cooperative Oncology Group >2.5) had better survival at 6 months.Conclusions: Patients with EGFR positivity had better survival with chemotherapy but worse with radiotherapy. Patients who took chemotherapy and had good performance status had better survival on multivariate analysis. We didn’t find any correlation between EGFR positivity and poor survival.

scholarly journals Inhibition of epidermal growth factor receptor (EGFR) expression by human cytomegalovirus correlates with an increase in the expression and binding of Wilms' Tumour 1 protein to the EGFR promoter

2009 ◽  
Vol 90 (7) ◽  
pp. 1569-1574 ◽  
Author(s):  
Insiya Jafferji ◽  
Mark Bain ◽  
Christine King ◽  
John H. Sinclair
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Cytomegalovirus ◽  
Growth Factor Receptor ◽  
Cell Surface Receptor ◽  
Wilms Tumour ◽  
Promote Cell Proliferation ◽  
Egfr Expression ◽  
Epidermal Growth

Infection with human cytomegalovirus (HCMV) modulates the expression of a number of cellular receptors and is known to inhibit expression of the epidermal growth factor receptor (EGFR), a cell surface receptor that can promote cell proliferation through a cascade of intracellular signalling events. We have examined the mechanisms by which HCMV mediates downregulation of EGFR expression and show that virus infection results in the profound upregulation of Wilms' Tumour 1 (WT1) protein, a transcription factor associated with the negative regulation of a number of growth factors and growth factor receptors, including EGFR. Moreover, chromatin immunoprecipitation experiments also show that HCMV infection results in increased binding of WT1 to the EGFR promoter. Finally, we show that depleting the cell of WT1 using small interfering RNA abrogates virus-mediated downregulation of EGFR. Taken together, our observations suggest that HCMV-mediated repression of EGFR expression results from a virus-mediated increase in cellular WT1, a known pleiotropic regulator of mitogenesis, apoptosis and differentiation.

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