scholarly journals Transcriptomic study of the mechanism of anoikis resistance in head and neck squamous carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6978
Author(s):  
Chen Guo ◽  
Ling-feng Xu ◽  
Hui-min Li ◽  
Wei Wang ◽  
Ji-hua Guo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Squamous Carcinoma ◽  
Enrichment Analysis ◽  
Anoikis Resistance ◽  
Vegf Signaling ◽  
Go Enrichment ◽  
Gene Correlation ◽  
Vegf Signaling Pathway

Background Normal epithelial cells rapidly undergo apoptosis as soon as they lose contact with the extracellular matrix (ECM), which is termed as anoikis. However, cancer cells tend to develop a resistance mechanism to anoikis. This acquired ability is termed as anoikis resistance. Cancer cells, with anoikis resistance, can spread to distant tissues or organs via the peripheral circulatory system and cause cancer metastasis. Thus, inhibition of anoikis resistance blocks the metastatic ability of cancer cells. Methods Anoikis-resistant CAL27 (CAL27AR) cells were induced from CAL27 cells using the suspension culture approach. Transcriptome analysis was performed using RNA-Seq to study the differentially expressed genes (DEGs) between the CAL27ARcells and the parental CAL27 cells. Gene function annotation and Gene Ontology (GO) enrichment analysis were performed using DAVID database. Signaling pathways involved in DEGs were analyzed using Gene Set Enrichment Analysis (GSEA) software. Analysis results were confirmed by reverse transcription PCR (RT-PCR), western blotting, and gene correlation analysis based on the TCGA database. Results GO enrichment analysis indicated that the biological process (BP) of the DEGs was associated with epidermal development, DNA replication, and G1/S transition of the mitotic cell cycle. The analysis of cellular component (CC) showed that the most significant up-regulated genes were related to extracellular exosome. KEGG Pathway analysis revealed that 23 signaling pathways were activated (p-value ≤ 0.05, FDR q-value ≤ 0.05) and 22 signaling pathways were suppressed (p-value ≤ 0.05, FDR q-value ≤ 0.05). The results from the GSEA indicated that in contrast to the inhibition of EGFR signaling pathway, the VEGF signaling pathway was activated. The VEGF signaling pathway possibly activates STAT3 though induction of STAT3 phosphorylation. Gene correlation analysis revealed that the VEGFA- STAT3-KLF4-CDKN1A signal axis was not only present in head and neck squamous carcinoma (HNSCC) but also two other epithelial-derived carcinomas that highly express VEGFA, including kidney renal clear cell carcinoma (KIRC) and ovarian serous cystadenocarcinoma (OV).

PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells

2009 ◽  
Vol 331 (1-2) ◽  
pp. 161-171 ◽  
Author(s):  
Jiachi Ma ◽  
Hirozumi Sawai ◽  
Nobuo Ochi ◽  
Yoichi Matsuo ◽  
Donghui Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Pancreatic Cancer ◽  
Vegf Signaling ◽  
Pancreatic Cancer Cells ◽  
Vegf Signaling Pathway

Tivantinib inhibits the VEGF signaling pathway and induces apoptosis in gastric cancer cells with c-MET or VEGFA amplification

2020 ◽  
Vol 38 (6) ◽  
pp. 1633-1640 ◽  
Author(s):  
Bum Jun Kim ◽  
Yoo Jin Kim ◽  
Sung-Hwa Sohn ◽  
Bohyun Kim ◽  
Hee Jung Sul ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

scholarly journals Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Haixiong Lin ◽  
Xiaotong Wang ◽  
Ligang Wang ◽  
Hang Dong ◽  
Peizhen Huang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Protein Targets ◽  
Pathway Enrichment ◽  
Vegf Signaling ◽  
Synergistic Mechanism

Background. Drynariae Rhizoma (DR) has been widely used in the prevention and treatment of various fractures. However, the specific mechanisms of DR’s active ingredients have not been elucidated. The purpose of this study was to explore the synergistic mechanisms of DR for treating fracture. Methods. A network pharmacology approach integrating ingredient screening, target exploration, active ingredients-gene target network construction, protein-protein interaction network construction, molecular docking, gene-protein classification, gene ontology (GO) functional analysis, KEGG pathway enrichment analysis, and signaling pathway integration was used. Results. This approach identified 17 active ingredients of DR, interacting with 144 common gene targets and 143 protein targets of DR and fracture. NCOA1, GSK3B, TTPA, and MAPK1 were identified as important gene targets. Five most important protein targets were also identified, including MAPK1, SRC, HRAS, RXRA, and NCOA1. Molecular docking found that DR has a good binding potential with common protein targets. GO functional analysis indicated that common genes involve multiple processes, parts and functions in biological process, cellular component, and molecular function, including positive regulation of transcription from RNA polymerase II promoter, signal transduction, cytosol, extracellular exosome, cytoplasm, and protein binding. The KEGG pathway enrichment analysis indicated that common gene targets play a role in repairing fractures in multiple signaling pathways, including MAPK, PI3K/AKT, Ras, and VEGF signaling pathways. MAPK and PI3K/AKT signaling pathways were involved in osteoblast formation, Ras signaling pathway was involved in enhancing mesenchymal stromal cell migration, and VEGF signaling pathway was involved in angiogenesis. Conclusion. The study revealed the correlation between DR and fracture and the potential synergistic mechanism of different targets of DR in the treatment of fractures, which provides a reference for the development of new drugs.

scholarly journals RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Baoling Liu ◽  
Quanping Su ◽  
Bolian Xiao ◽  
Guodong Zheng ◽  
Lizhong Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
Gene Set Enrichment Analysis ◽  
Signal Pathways ◽  
Vegf Signaling ◽  
Gene Functions ◽  
Vegf Signaling Pathway

Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways.

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