scholarly journals Time series expression pattern of key genes reveals the molecular process of esophageal cancer

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Jiafu Wang ◽  
Xiang Xie ◽  
Yurong Sun
Keyword(s):  
Esophageal Cancer ◽  
Survival Analysis ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Protein Transport ◽  
Differential Expression Analysis ◽  
Growth Factor Receptor ◽  
Gene Interaction ◽  
Molecular Process ◽  
Egfr Signaling Pathway

Abstract Background: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease is still elusive. Aim: To investigate the molecular process of esophageal cancer comprehensively and deeply. Methods: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer. Then exacting gene interaction modules and hub genes were identified in module interaction network. Further, though survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related function or pathway were identified to elucidate potential mechanism in esophageal cancer. Results: A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding and other biological processes (BPs), as well as p53 signaling pathway, ERBB signaling pathway and epidermal growth factor receptor (EGFR) signaling pathway. Then, transcription factors (TFs) (including HIF1A) and ncRNAs (including CRNDE and hsa-mir-330-3p) significantly regulate dysfunction modules were identified. Further, survival analysis showed that GNGT2 was closely related to survival of esophageal cancer. And DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Conclusion: These works not only help us to reveal the potential regulatory factors in the development of disease, but also deepen our understanding of its deterioration mechanism.

scholarly journals Transactivation of Platelet-Derived Growth Factor Receptor α by the GTPase-Deficient Activated Mutant of Gα12

2006 ◽  
Vol 26 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Rashmi N. Kumar ◽  
Ji Hee Ha ◽  
Rangasudhagar Radhakrishnan ◽  
Danny N. Dhanasekaran
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Dominant Negative Mutant ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT The GTPase-deficient, activated mutant of Gα12 (Gα12Q229L, or Gα12QL) induces neoplastic growth and oncogenic transformation of NIH 3T3 cells. Using microarray analysis, we have previously identified a role for platelet-derived growth factor receptor α (PDGFRα) in Gα12-mediated cell growth (R. N. Kumar et al., Cell Biochem. Biophys. 41:63-73, 2004). In the present study, we report that Gα12QL stimulates the functional expression of PDGFRα and demonstrate that the expression of PDGFRα by Gα12QL is dependent on the small GTPase Rho. Our results indicate that it is cell type independent as the transient expression of Gα12QL or the activation of Gα12-coupled receptors stimulates the expression of PDGFRα in NIH 3T3 as well as in human astrocytoma 1321N1 cells. Furthermore, we demonstrate the presence of an autocrine loop involving PDGF-A and PDGFRα in Gα12QL-transformed cells. Analysis of the functional consequences of the Gα12-PDGFRα signaling axis indicates that Gα12 stimulates the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway through PDGFR. In addition, we show that Gα12QL stimulates the phosphorylation of forkhead transcription factor FKHRL1 via AKT in a PDGFRα- and PI3K-dependent manner. Since AKT promotes cell growth by blocking the transcription of antiproliferative genes through the inhibitory phosphorylation of forkhead transcription factors, our results describe for the first time a PDGFRα-dependent signaling pathway involving PI3K-AKT-FKHRL1, regulated by Gα12QL in promoting cell growth. Consistent with this view, we demonstrate that the expression of a dominant negative mutant of PDGFRα attenuated Gα12-mediated neoplastic transformation of NIH 3T3 cells.

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 The p38 signaling pathway mediates quiescence of glioma stem cells by regulating epidermal growth factor receptor trafficking

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33316-33328 ◽  
Author(s):  
Akio Soeda ◽  
Justin Lathia ◽  
Brian J. Williams ◽  
Qiulian Wu ◽  
Joseph Gallagher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Receptor Trafficking ◽  
Glioma Stem Cells ◽  
Epidermal Growth

scholarly journals Advances in targeted therapy for esophageal cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yan-Ming Yang ◽  
Pan Hong ◽  
Wen Wen Xu ◽  
Qing-Yu He ◽  
Bin Li
Keyword(s):  
Esophageal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Targeted Therapies ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Immune Checkpoints ◽  
Her 2 ◽  
Epidermal Growth

Abstract Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

Sign in / Sign up

Export Citation Format

Share Document