KIF26B promotes proliferation and metastasis by activating the VEGF signaling pathway in gastric cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72307 | GEO | 2017/09/01
SECONDARY ACCESSION(S): PRJNA293698
REPOSITORIES: GEO
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Project description:KIF26B promotes proliferation and metastasis by activating the VEGF signaling pathway in gastric cancer
| PRJNA293698 | ENA
Project description:BackgroundAs a member of the ERM (ezrin-radixin-moesin) protein family, EZR has been recognized as a regulator of adhesion signal pathways by researchers. Moreover, EZR was thought to play irreplaceable roles in invasion and metastasis of versatile cancers. In this study, we managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC).MethodsTo analyze the impact of EZR expression on overall survival and free diseases survival of PC patients, we screened abnormally expressed EZR in PC using the Gene Expression Omnibus database (GEO database) and The Cancer Genome Atlas (TCGA) database. Following, Gene Ontology (GO)-based functional analysis and Gene set enrichment analysis (GSEA) was performed to predicate the possible biological processes in which EZR were involved. The clinicopathological characteristics and prognosis of PC patients were analyzed according to clinical data. Further, immunohistochemistry, western blotting and real time PCR analysis were conducted to analyze the expression level of EZR in PC and paired paracancerous tissues. The effect of EZR on proliferation of PC cell lines were detected by Cell Counting Kit-8 assay, and meanwhile, Transwell assay was performed to detect the effect of EZR on invasion and migration of PC cell.ResultEZR exhibited higher expression level in pancreatic cancer tissues and cell than paracancerous tissues and cell, and its expression level was positively correlated with poor overall survival and diseases-free survival in PC patients. CCK8 assay indicated that EZR facilitated the proliferation of PC cells, meanwhile, Transwell assay showed that EZR promoted the migration and invasion of PC cells. The GO analysis predicated that EZR was involved in biological processes including cell adhesion, ameboidal-type cell migration, cell junction assembly. Through GSEA analysis, pancreatic cancer pathway, and the adhesion junction pathway were screened as the mostly enriched pathways in EZR-regulated pathological process. The inhibition of EZR suppressed proliferation and migration of PC cells. Western blot experiment revealed a positive correlation between EZR and FAK, the proliferation invasion and migration ability of PC cells were significantly decreased after knockdown of EZR.ConclusionOur finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway.
| S-EPMC8502343 | biostudies-literature
Project description:Lymph node metastasis confers an unfavorable prognosis in gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but the changes of expression profiling of metastatic GC in lymph nodes remain largely unknown. To identify the potential driver genes, we performed whole transcriptomic sequencing (RNA-seq) on five pairs of gastric adenocarcinoma specimens with metastatic lymph nodes confirmed by pathology. We identified six genes associated with lymph node metastasis and predicted poor prognosis in GC patients. Finally, we focused on PRICKLE1, a cell polarity protein, which dramatically upregulated in several GC cell lines from metastatic lesions compared with those from the primary tumor. Loss and gain of function assay in vitro showed that the migration and invasion capability of GC cells were limited by downregulating and upregulating PRICKLE1 expression. Mechanically, we found PRICKLE1 might modulate tumor metastasis through mTOR signaling pathway. Inhibition of mTOR significantly reduced GC cell migration and invasion in vitro. In summary, we identified and validated PRICKLE1 as a novel gene involved in GC metastasis. This study provided a valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination.
| S-EPMC8205837 | biostudies-literature
Project description:Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide, with extremely poor prognosis. Recently, forkhead box k1 (FOXK1), a member of the FOX transcription factor family, has been reported to be correlated with tumor progression in multiple malignancies. However, the role of FOXK1 in GBC has not been elucidated. In this study, we demonstrated that the expression level of FOXK1 was elevated in human GBC tissues and associated with increased liver metastasis, poor histological differentiation, advanced TNM stage, and shorter overall survival. Knockdown of FOXK1 expression inhibited GBC cells proliferation and metastasis. Consistently, overexpression of FOXK1 promoted GBC cells progression. Mechanical investigations verified that knockdown of FOXK1 could lead to G1/S cell cycle arrest through downregulating CDK4, CDK6, cyclin D1, and cyclin E1. And FOXK1 could regulate the expression of epithelial-mesenchymal transition (EMT) related proteins E-cad, N-cad, and Vimentin. Moreover, we found that FOXK1 could regulate the activation of Akt/mTOR signaling pathway. In addition, AKT special inhibitor MK-2206 could abolish the proliferation and metastasis discrepancy between FOXK1 overexpression GBC cells and control cells, which suggested the tumorpromoting effect of FOXK1 may be partially related with the activations of Akt/mTOR signaling pathway. Collectively, our results suggested that FOXK1 promotes GBC cells progression and represent a novel prognostic biomarker and potential therapeutic target in GBC.
| S-EPMC7180204 | biostudies-literature
Project description:The vascular endothelium plays an essential role in vascular disease and cardiovascular diseases. The effects and underlying mechanisms of sevoflurane on vascular endothelial growth factor (VEGF) in human endothelial cells have not been elucidated. The MTT colorimetric assay was used to determine HUVEC activity at different concentrations (1 and 3%, respectively) of sevoflurane for different time-points (12, 24 and 48 h, respectively). The regulation of sevoflurane on the mRNA levels of VEGFa, VEGFb, VEGFc and VEGFR1, 2, 3 was analyzed by real-time PCR. When VEGFR2 was inhibited by axitinib, VEGFR2 protein expression was determined by western blotting, and the cell viability was assessed by MTT analysis. The results revealed that sevoflurane increased cell viability in a dose- and time-dependent manner. Sevoflurane significantly upregulated VEGFA mRNA expression only. In addition, sevoflurane increased the expression of VEGFR2 at the mRNA and protein levels, whereas sevoflurane did not modulate the mRNA expression of VEGFR1 and VEGFR3. Furthermore, sevoflurane failed to increase the mRNA and protein expression of VEGFR2 when VEGFR2 was inhibited by axitinib, an inhibitor of VEGF receptors. In conclusion, sevoflurane may be a promising agent against endothelium dysfunction-caused vascular disease by activating the VEGF-A/VEGFR2 signaling pathway.
| S-EPMC6966126 | biostudies-literature
Project description:Ubiquitin-associated protein 2-like (UBAP2L) is highly expressed in various types of tumors and has been shown to participate in tumor growth and metastasis; however, its role in gastric cancer (GC) remains unknown. In this study, we observed that UBAP2L expression was markedly elevated in GC tissues and five GC cell lines. Higher expression of UBAP2L was associated with poor prognosis as revealed by bioinformatics analysis on online websites and laboratory experiments. Knockdown of UBAP2L impeded the migration and invasion abilities of GC cell lines. In contrast, its overexpression enhanced the migration and invasion abilities of GC cell lines. Overexpression of UBAP2L also increased the number and size of lung metastatic nodules in vivo. According to the results of mass spectrometry and pathway annotation of the identified proteins, the PI3K/AKT pathway was found to be related to UBAP2L regulation. Further exploration and rescue experiments revealed that UBAP2L stimulates the expression and nuclear aggregation of p65 and promotes the expression of SP1 by activating the PI3K/AKT pathway. In summary, our findings indicate that UBAP2L regulates GC metastasis through the PI3K/AKT/SP1/NF-κB axis. Thus, targeting UBAP2L may be a potential therapeutic strategy for GC.
| S-EPMC8933503 | biostudies-literature
Project description:BackgroundTumor cells produce vascular endothelial growth factor (VEGF) which interact with the membrane or cytoplasmic VEGF receptors (VEGFRs) to promote cell growth in an angiogenesis-independent fashion. Apatinib, a highly selective VEGFR2 inhibitor, is the only effective drug for patients with terminal gastric cancer (GC) who have no other chemotherapeutic options. However, its treatment efficacy is still controversy and the mechanism behind remains undetermined. In this study, we aimed to investigate the role of autocrine VEGF signaling in the growth of gastric cancer cells and the efficacy of Apatinib treatment.MethodsThe expression of phosphor VEGFR2 in gastric cancer cell lines was determined by real-time PCR, immunofluorescence, and Western blot. The gastric cancer cells were administrated with or without recombination human VEGF (rhVEGF), VEGFR2 neutralizing antibody, U73122, SU1498, and Apatinib. The nude mice were used for xenograft tumor model.Resultswe found that autocrine VEGF induced high VEGFR2-expression, promoted phosphorylation of VEGFR2, and further enhanced internalization of pVEGFR2 in gastric cancer cells. The autocrine VEGF was self-sustained through increasing VEGF mRNA and protein expression. It exerted pro-proliferative effect through a PLC-ERK1/2 dependent pathway. Furthermore, we demonstrated that in VEGFR2 overexpressing gastric cancer cells, Apatinib inhibited cell proliferation in vitro and delayed xenograft tumor growth in vivo. However, these effects were not observed in VEGFR2 low expressing gastric cancer cells.ConclusionThese results suggested that autocrine VEGF signaling promotes gastric cancer cell proliferation and enhances Apatinib treatment outcome in VEGFR2 overexpression gastric cancer cells both in vitro and in vivo. This study would enable better stratification of gastric cancer patients for clinical treatment decision.
| S-EPMC5355320 | biostudies-literature
Project description:Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value.
| S-EPMC4900635 | biostudies-literature
Project description:Background:Gastric cancer (GC) is one common cancer which occurs in the stomach leading to high mortality around the world. Long non-coding RNAs (lncRNAs) were found overexpressed or silenced in the occurrence and progression of multiple cancers including GC. Method:The gene expression level in GC tissues and cells were analyzed by RT-qPCR. CCK-8, colony formation, flow cytometry and transwell assays were performed for the function analysis of HLA complex group 11 (HCG11). The mechanism study for HCG11 was conducted using RIP, RNA pull down and luciferase reporter assays. Results:HCG11 was discovered highly expressed in GC tissues and cells. Depletion experiments were used to evaluate HCG11 silence on cell proliferation, migration and apoptosis. Moreover, Wnt signaling pathway was found as a tumor promoter in GC. RIP assay, RNA pull down assay and luciferase reporter assay were performed to illustrate the relationship of HCG11, miR-1276 and CTNNB1. Rescue assays revealed that HCG11/miR-1276/CTNNB1 axis regulated the incidence and development of GC. Tumor formation in mice proved that HCG11 was negatively correlated with miR-1276 and had positively correlation with CTNNB1. Conclusion:Overall, HCG11 accelerated proliferation and migration in GC through miR-1276/CTNNB1 and Wnt signaling pathway, revealing that HCG11 could be a brand new target for GC.
| S-EPMC6933929 | biostudies-literature
Project description:ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.
| S-EPMC8436930 | biostudies-literature