Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PGE2 promotes renal carcinoma cell invasion through activated RalA.

ABSTRACT: Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral·GTP inactivator RGC2. The results support the idea that targeted interference of EP2/EP4 signal to RalA·GTP may provide benefit to patients diagnosed with advanced kidney cancer.

SUBMITTER: Li Z

PROVIDER: S-EPMC3421051 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

PGE2 promotes renal carcinoma cell invasion through activated RalA.

Li Z Z Zhang Y Y Kim W J WJ Daaka Y Y

Oncogene 20120514 11

Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral·GTP inactivator RGC2. T ...[more]

PMID: 22580611

Similar Datasets

ANXA13 promotes cell proliferation and invasion and attenuates apoptosis in renal cell carcinoma.

Project description:PurposeEmerging evidences have demonstrated that annexin A13 (ANXA13) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of ANXA13 in Clear cell renal cell carcinoma (ccRCC) have not been defined. Therefore, this study aimed to clarify the potential role of ANXA13 in regulating the proliferation, migration, invasion, cell cycle, and apoptosis of ccRCC cells.Patients and methodsThe quantitative real-time PCR (qRT-PCR) and western blotting was performed for detecting the ANXA13 expression in ccRCC tissues at the mRNA and protein levels, respectively. The GEPIA2 databases were used to derive data for analyzing the ANXA13 expression in pan-cancer and ccRCC clinical features. Cell Counting and colony formation assays, as well as flow cytometry, were used to detect cell proliferation, apoptosis, or cell cycle. The wound healing assay was used to evaluate the migration ability of cells, and the Trans-well assay was conducted to determine the cell invasiveness.ResultsANXA13 was upregulated in ccRCC cells and human ccRCC tissues. Furthermore, siANXA13 inhibited ccRCC cell proliferation, migration, invasion and induced cell apoptosis.ConclusionANXA13 was upregulated in ccRCC. ANXA13 promotes tumorigenic traits of ccRCC cell lines in vitro. ANXA13 is a potential novel biomarker and a potential therapeutic target in ccRCC.

| S-EPMC10374933 | biostudies-literature

CIP2A Promotes Proliferation, Invasion and Chemoresistance to Cisplatin in Renal Cell Carcinoma.

Project description:CIP2A is a well-known oncoprotein whose expression is elevated in multiple human solid tumor types. However, its role in renal cell carcinoma (RCC) development is poorly understood. Thus, in our present study, we used the renal cancer cell lines 786-O, A498 and CAKI-1 and the renal epithelial cell line HK-2 to clarify the function of CIP2A in RCC. We found that CIP2A expression is much higher in the RCC cells than in the normal renal epithelial cell. Lentivirus covered coding region CIP2A cDNA sequence and CIP2A siRNA were used to up and down regulate CIP2A expression in vitro. We found that overexpression of CIP2A promoted G1/S transition and cell proliferation. In addition, up-regulation of CIP2A significantly enhanced the invasion and migration capabilities of the cells. Furthermore, CIP2A promoted epithelial-mesenchymal transformation (EMT) and chemoresistance to cisplatin in RCC cells. Taken together, our findings demonstrate that CIP2A plays an important role in proliferation, invasion and chemoresistance to cisplatin in RCC cells. CIP2A may serve as an ideal molecular target for RCC therapeutics.

| S-EPMC6218763 | biostudies-literature

ELOVL5 promotes cell proliferation and invasion in renal cell carcinoma

Project description:Fatty acid is a main component of lipid. The differences of chain-length and pattern of saturation / desaturation in fatty acid are essential for diversity of biological lipid functions. Elongation of very-long-chain fatty acids (ELOVL) plays a critical role in regulating the elongation of fatty acid and ELOVL 1 to 7 are reported in the present. In several cancers but renal cell carcinoma (RCC), the relationship between ELOVLs and cancer progression has been reported. In TCGA cohort, ELOVL5 expression is associated with advanced TNM stage and poor prognosis. We performed CRISPR-Cas9 targeted knockout of ELOVL5 in 2 different RCC cell lines, ACHN and 786-O, respectively. ELOVL5 knockout significantly suppressed cellular invasion, migration and proliferation in vitro and in vivo. In ingenuity Pathway Analysis, Akt signaling activation was decreased in ELOVL5-KO cells. In western blotting analysis, the phosphorylation level of Akt was inhibited in ELOVL5-KO cells. Resultantly, it was suggested that ELOVL5 is involved in the phosphorylation level of Akt and affects cancer progression in RCC.

2022-08-17 | GSE192403 | GEO

Transforming growth factor-β promotes aggressiveness and invasion of clear cell renal cell carcinoma.

Project description:The molecular mechanisms whereby transforming growth factor-β (TGF-β) promotes clear cell renal cell carcinoma (ccRCC) progression is elusive. The cell membrane bound TGF-β type I receptor (ALK5), was recently found to undergo proteolytic cleavage in aggressive prostate cancer cells, resulting in liberation and subsequent nuclear translocation of its intracellular domain (ICD), suggesting that ALK5-ICD might be a useful cancer biomarker. Herein, the possible correlation between ALK5 full length (ALK5-FL) and ALK5-ICD protein, phosphorylated Smad2/3 (pSmad2/3), and expression of TGF-β target gene PAI-1, was investigated in a clinical ccRCC material, in relation to tumor grade, stage, size and cancer specific survival. Expression of ALK5-FL, ALK5-ICD, pSmad2/3 and PAI-1 protein levels were significantly higher in higher stage and associated with adverse survival. ALK5-ICD, pSmad2/3 and PAI-1 correlated with higher grade, and ALK5-FL, pSmad2/3 and PAI-1 protein levels were significantly correlated with larger tumor size. Moreover, the functional role of the TGF-β - ALK5-ICD pathway were investigated in two ccRCC cell lines by treatment with ADAM/MMP2 inhibitor TAPI-2, which prevented TGF-β-induced ALK5-ICD generation, nuclear translocation, as well as cell invasion. The present study demonstrated that canonical TGF-β Smad2/3 pathway and generation of ALK5-ICD correlates with poor survival and invasion of ccRCC in vitro.

| S-EPMC5094972 | biostudies-literature

miR-1179 promotes cell invasion through SLIT2/ROBO1 axis in esophageal squamous cell carcinoma.

Project description:MiR-1179, a new identified miRNA highly associated with metastasis of colorectal cancer which was never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of miR-1179 and the candidate target gene in tissues from 40 patients with ESCC. Transwell, Dual-luciferase reporter assay and immunocytochemistry assay were employed to detect the function role of miR-1179 in vitro. We found that miR-1179 was up-regulated in human ESCC tumor tissues. Bioinformatics analysis indicated that SLIT2 acting as a new potential target of miR-1179 which was confirmed by luciferase reporter assay. Down-regulation of miR-1179 suppressed cell invasion in vitro with an increasing level of SLIT2 and ROBO1, besides, the up-regulation of SLIT2 decreased cell invasion through ROBO1. Taken together, these findings will shed light the role to mechanism of miR-1179 in regulating cell invasion via SLIT2/ROBO1 axis.

| S-EPMC4348900 | biostudies-other

SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma.

Project description:SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this study, SLC17A9 was initially identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Then, the aberrant expression levels of SLC17A9 were confirmed in both the cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, thus promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion activity of renal cancer cells, whereas its overexpression led to stronger cell viability and more malignant phenotype in vitro. The overexpression of SLC17A9 in vivo could significantly contribute to the growth of tumors. Finally, we found that SLC17A9 might be related to the drug resistance of vorinostat. Cumulatively, this study demonstrated that the SLC17A9-PTHLH-EMT axis could promote the progression of ccRCC.

| S-EPMC9800294 | biostudies-literature

β-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma.

Project description:β-Catenin (CTNNB1 gene coding protein) is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of β-catenin in renal cell carcinoma (RCC) cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.

| S-EPMC5328321 | biostudies-literature

Nox4 mediates renal cell carcinoma cell invasion through hypoxia-induced interleukin 6- and 8- production.

Project description:Inflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro-inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated.We have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion.Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC.

| S-EPMC3267761 | biostudies-literature

piRNA-31115 Promotes Cell Proliferation and Invasion via PI3K/AKT Pathway in Clear Cell Renal Carcinoma.

Project description:PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that play important roles in germline development and carcinogenesis. In this study, we used the deep sequencing of small RNA Transcriptome to explore the piRNA expression in six clear cell renal carcinoma (ccRCC) tissues and matched adjacent normal tissues and found that six piRNAs were upregulated and sixteen were downregulated in ccRCC tissues. Among them, piRNA-31115 (NCBI accession number: DQ571003) was the most upregulated piRNA in ccRCC tissues compared with matched adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to confirm piR-31115 expression in other ccRCC tissues (n = 40) and ccRCC cell lines. Besides, function analysis demonstrated that silencing of piR-31115 inhibited ccRCC cell proliferation, motility, and invasiveness. Mechanistic investigations showed that piRNA-31115 may activate epithelial-mesenchymal transition (EMT) via the PI3K/AKT signaling pathway. Hence, piR-31115 may represent an oncogene in the development of ccRCC.

| S-EPMC8592738 | biostudies-literature