scholarly journals CAF promotes chemoresistance through NRP2 in gastric cancer

2021 ◽  
Author(s):  
Yanpeng Yang ◽  
Yongchen Ma ◽  
Shen Yan ◽  
Pengyuan Wang ◽  
Jianwen Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Hippo Pathway ◽  
Bioactive Molecules ◽  
Specific Cell ◽  
Gastric Cancer Cells ◽  
Gastric Cancers ◽  
Stromal Cell Derived Factor ◽  
Gastric Cancer Patients

Abstract Background Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. Methods Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. Results CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. Conclusions The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.

scholarly journals DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3463
Author(s):  
Sheng-Fan Wang ◽  
Kuo-Hung Huang ◽  
Wei-Chuan Tseng ◽  
Jeng-Fan Lo ◽  
Anna Fen-Yau Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Gastric Cancers ◽  
Gastric Cancer Patients

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. Methods: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. Results: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown–induced cell migration and invasion of gastric cancer cells. Conclusions: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.

scholarly journals Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jingjing Zhang ◽  
Jun Xu ◽  
Yonghong Dong ◽  
Bo Huang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Vegf Expression ◽  
Gastric Cancer Cells ◽  
Tumor Tissues ◽  
Sirna Silencing ◽  
Gastric Cancer Patients

In view of the high incidence of gastric cancer and the functions of hypoxia-inducible factor 1α (HIF-1α), our study aimed to investigate the functionality of HIF-1α in gastric cancer, and to explore the diagnostic and prognostic values of HIF-1α for this disease. Expression of HIF-1α in tumor tissues and adjacent healthy tissues as well as serum collected from both gastric cancer patients and normal healthy controls was detected by qRT-PCR. Survival analysis was performed using Kaplan–Meier method. HIF-1α siRNA silencing cell lines were established. Effects of HIF-1α siRNA silencing as well as PI3K activator sc3036 on proliferation, migration, and invasion of gastric cancer cells were detected by Cell counting kit (CCK-8) assay, and Transwell migration and invasion assay. Effects of HIF-1α siRNA silencing on AKT and VEGF were detected by Western blot. Expression of HIF-1α was significantly down-regulated in tumor tissues than in adjacent healthy tissues in most gastric cancer patients. Serum levels of HIF-1α were also higher in gastric cancer patients than in normal healthy people. Serum HIF-1α showed promising diagnostic and prognostic values for gastric cancer. HIF-1α siRNA silencing inhibited the proliferation, migration, and invasion of gastric cancer cells, while PI3K activator sc3036 treatment reduced those inhibitory effects. Down-regulation of HIF-1α can inhibit the proliferation, migration, and invasion of gastric cancer possibly by inhibiting PI3K/AKT pathway and VEGF expression.

scholarly journals Activating Hippo Pathway via Rassf1 by Ursolic Acid Suppresses the Tumorigenesis of Gastric Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4709 ◽  
Author(s):  
Seong-Hun Kim ◽  
Hua Jin ◽  
Ruo Yu Meng ◽  
Da-Yeah Kim ◽  
Yu Chuan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Hippo Pathway ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Protein Levels ◽  
Tumor Tissues ◽  
The Hippo Pathway

The Hippo pathway is often dysregulated in many carcinomas, which results in various stages of tumor progression. Ursolic acid (UA), a natural compound that exists in many herbal plants, is known to obstruct cancer progression and exerts anti-carcinogenic effect on a number of human cancers. In this study, we aimed to examine the biological mechanisms of action of UA through the Hippo pathway in gastric cancer cells. MTT assay showed a decreased viability of gastric cancer cells after treatment with UA. Following treatment with UA, colony numbers and the sizes of gastric cancer cells were significantly diminished and apoptosis was observed in SNU484 and SNU638 cells. The invasion and migration rates of gastric cancer cells were suppressed by UA in a dose-dependent manner. To further determine the gene expression patterns that are related to the effects of UA, a microarray analysis was performed. Gene ontology analysis revealed that several genes, such as the Hippo pathway upstream target gene, ras association domain family (RASSF1), and its downstream target genes (MST1, MST2, and LATS1) were significantly upregulated by UA, while the expression of YAP1 gene, together with oncogenes (FOXM1, KRAS, and BATF), were significantly decreased. Similar to the gene expression profiling results, the protein levels of RASSF1, MST1, MST2, LATS1, and p-YAP were increased, whereas those of CTGF were decreased by UA in gastric cancer cells. The p-YAP expression induced in gastric cancer cells by UA was reversed with RASSF1 silencing. In addition, the protein levels in the Hippo pathway were increased in the UA-treated xenograft tumor tissues as compared with that in the control tumor tissues; thus, UA significantly inhibited the tumorigenesis of gastric cancer in vivo in xenograft animals. Collectively, UA diminishes the proliferation and metastasis of gastric cancer via the regulation of Hippo pathway through Rassf1, which suggests that UA can be used as a potential chemopreventive and therapeutic agent for gastric cancer.

Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Yu Jin Kim ◽  
Won Shik Kim ◽  
Sang Woo Kim ◽  
Woon Yong Jung
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Gastric Adenoma ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Gastric Cancer Patients ◽  
And Function

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

scholarly journals Propofol Stimulates Immune Activity and Decreases Inflammatory Cytokines via NF-κB-Mediated JAK1-STAT3 Pathway in Gastric Cancer Patients Undergoing Radical Surgery

2020 ◽  
Author(s):  
Haili Zhang ◽  
Shi Qian ◽  
Wang Jing
Keyword(s):  
Gastric Cancer ◽  
General Anesthesia ◽  
Immune Function ◽  
Cancer Cells ◽  
Radical Surgery ◽  
Serum Concentrations ◽  
Gastric Cancer Cells ◽  
Tnf Α ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract BackgroundPropofol is the most commonly used general anesthesia for patients with gastric cancer undergoing radical surgery. Studies have suggested that propofol exerts beneficial effects on the immune function of patients with cancer. However, the potential mechanism underlying propofol-mediated immune regulation remains to be elucidated. The present study investigated the regulatory effects of propofol on immune function in patients with gastric cancer undergoing radical surgery. MethodsELISA, reverse transcription-quantitative polymerase chain reaction, western blotting, gene transfection and immunohistochemistry were used to analyze the effects of propofol on gastric cancer cells.ResultsResults demonstrated that propofol general anesthesia resulted in an increased percentage of cluster of differentiation (CD)4+ and CD8+ cells, increased serum concentrations of interleukin (IL)-2 and tumor necrosis factor (TNF)-α, decreased serum concentrations of IL-1β and IL-8 following propofol general anesthesia in gastric cancer patients undergoing radical surgery compared with midazolam. In addition, propofol general anesthesia induced an imbalance in T helper (Th)1/Th2 cells, increased the number of natural killer cells and B cells, decreased the expression of prognostic factors, and improved tumor metastasis, recurrence and survival in patients with gastric cancer compared with midazolam. Furthermore, immunohistochemistry demonstrated that propofol downregulated nuclear factor (NF)-κBp65, and upregulated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) expression level in gastric cancer tissues, downregulated the protein expression levels of NF-κBp65, JAK1, STAT3, TNF-α, IL-1β and IL-8 protein expression in gastric cancer cells isolated from gastric cancer tissues. NF-κBp65 overexpression inhibited propofol-mediated upregulation of JAK1, STAT3, TNF-α, IL-1β and IL-8 expression in gastric cancer cells. ConclusionsThese data indicate that that propofol may increase the number of T cells, stimulate T-cell proliferation, upregulate IL-2 and TNF-α expression, and enhance immune function via the NF-κB-mediated JAK1-STAT3 signaling pathway in patients with gastric cancer undergoing radical surgery.

scholarly journals UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jian-Xian Lin ◽  
Xin-Sheng Xie ◽  
Xiong-Feng Weng ◽  
Sheng-Liang Qiu ◽  
Changhwan Yoon ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Gastric Cancer Patients

Abstract Background UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. Methods Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. Results Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. Conclusion UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

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