Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of hypoxia in pancreatic cancer invasion and metastasis.

ABSTRACT: Intratumoral hypoxia is a common feature of solid tumors. Recent advances in cancer biology indicate that hypoxia is not only a consequence of unrestrained tumor growth, but also plays an active role in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia signaling is mediated by the hypoxia-inducible factors (HIFs), which are not only stabilized under hypoxia, but also by activated oncogenes or inactivated tumor suppressors under normoxia. Hypoxia is a prominent feature of the tumor microenvironment of pancreatic tumors, also characterized by the presence of a fibrotic reaction that promotes, and is also modulated by, hypoxia. As the mechanisms by which hypoxia signaling impacts invasion and metastasis in pancreatic cancer are being elucidated, hypoxia is emerging as a key determinant of pancreatic cancer malignancy as well as an important target for therapy. Herein we present an overview of recent advances in the understanding of the impact that hypoxia has in pancreatic cancer invasion and metastasis.

SUBMITTER: Yuen A

PROVIDER: S-EPMC5045059 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The impact of hypoxia in pancreatic cancer invasion and metastasis.

Yuen Angela A Díaz Begoña B

Hypoxia (Auckland, N.Z.) 20140716

Intratumoral hypoxia is a common feature of solid tumors. Recent advances in cancer biology indicate that hypoxia is not only a consequence of unrestrained tumor growth, but also plays an active role in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia signaling is mediated by the hypoxia-inducible factors (HIFs), which are not only stabilized under hypoxia, but also by activated oncogenes or inactivated tumor suppressors under normoxia. Hypoxia is a prominent feature o ...[more]

PMID: 27774469

Similar Datasets

Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

Project description:Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-?B activity, TUSC3 expression was found to be reversely correlated with NF-?B activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-?B activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.

| S-EPMC4752499 | biostudies-literature

Extracellular DNA in pancreatic cancer promotes cell invasion and metastasis.

Project description:Aggressive metastasis is the chief cause of the high morbidity and mortality associated with pancreatic cancer, yet the basis for its aggressive behavior remains elusive. Extracellular DNA (exDNA) is a recently discovered component of inflammatory tissue states. Here, we report that exDNA is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. exDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells but absent from normal pancreas cells. Strikingly, treatment of cancer cell cultures with DNase I to degrade DNA nonspecifically reduced metastatic characters associated with matrix attachment, migration, and invasion. We further assessed the role of exDNA in pancreatic cancer metastasis in vivo using an orthotopic xenograft model established by implantation of pancreatic cancer cells expressing firefly luciferase. Noninvasive bioluminescent imaging confirmed that DNase I treatment was sufficient to suppress tumor metastasis. Mechanistic investigations suggested the existence of a positive feedback loop in which exDNA promotes expression of the inflammatory chemokine CXCL8, which leads to higher production of exDNA by pancreatic cancer cells, with a significant reduction in CXCL8 levels achieved by DNase I treatment. Taken together, our results strongly suggest that exDNA contributes to the highly invasive and metastatic character of pancreatic cancer.

| S-EPMC3777608 | biostudies-literature

Hypoxia/lncRNA-AK123072/EGFR pathway induced metastasis and invasion in gastric cancer.

Project description:OBJECTIVE:To investigate the role of long noncoding RNAs (lncRNAs) in hypoxia-induced gastric cancer (GC) metastasis and invasion. METHODS:We investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction. The role of the targeting lncRNA was further detected by in vivo and in vitro assays. RESULTS:We found an lncRNA, AK123072, which was up-regulated by hypoxia. AK123072 was frequently up-regulated in GC samples and promoted GC migration and invasion in vivo and in vitro. Furthermore, AK123072 could mediate the metastasis of hypoxia-induced GC cells. Next, we identified EGFR, which was a metastasis-related gene regulated by AK123072. In addition, we found that the expression of EGFR was positively correlated with that of AK123072 in the clinical GC samples used in our study. Furthermore, we found that the EGFR gene CpG island methylation was significantly increased in GC cells depleted of AK123072. Intriguingly, EGFR expression was also increased by hypoxia, and EGFR up-regulation by AK123072 mediated hypoxia-induced GC cell metastasis. CONCLUSION:Our results identified hypoxia/lncRNA-AK123072/EGFR pathway in gastric cancer pathogenesis and this might help in the development of new therapeutics in clinics.

| S-EPMC4723753 | biostudies-literature

Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis.

Project description:Breast cancer patients with increased expression of hypoxia-inducible factors (HIFs) in primary tumor biopsies are at increased risk of metastasis, which is the major cause of breast cancer-related mortality. The mechanisms by which intratumoral hypoxia and HIFs regulate metastasis are not fully elucidated. In this paper, we report that exposure of human breast cancer cells to hypoxia activates epidermal growth factor receptor (EGFR) signaling that is mediated by the HIF-dependent expression of a disintegrin and metalloprotease 12 (ADAM12), which mediates increased ectodomain shedding of heparin-binding EGF-like growth factor, an EGFR ligand, leading to EGFR-dependent phosphorylation of focal adhesion kinase. Inhibition of ADAM12 expression or activity decreased hypoxia-induced breast cancer cell migration and invasion in vitro, and dramatically impaired lung metastasis after orthotopic implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice.

| S-EPMC8126789 | biostudies-literature

Genomic analysis of invasion-metastasis-related factors in pancreatic cancer cells.

Project description:Pancreatic cancer is known to be an extremely lethal neoplasm, one of the reasons being that pancreatic cancer itself has an extremely high potential of invasion-metastasis. In our previous study, two pancreatic cancer cell lines with a different potential for invasion-metastasis, PC-1 with a low potential and PC-1.0 with a high potential of invasion-metastasis after intrapancreatic transplantation, were established in a Syrian golden hamster. To determine the invasion-metastasis-related factors, a cDNA microarray that represented a set of 27,000 genes was hybridized with a labeled cDNA probe and screened for molecular profiling analysis. Furthermore, Gene Ontology and Pathway differential expression of candidate genes was further validated using RT-PCR. One hundred and forty-one differentially expressed genes (>3.0-fold change) were identified in the present study, including 46 up-regulated genes (e.g., nup107, tjp-2 and MMP-13) and 95 down-regulated genes (e.g., Spc21, plau and CD44) in the PC-1.0 cells. Our present results suggest that a highly organized and structured process of tumor invasion-metastasis exists in the pancreas. Analysis of gene expression profiles by cDNA microarray provides useful information for clarifying the mechanism underlying this invasion and metastasis. Furthermore, the identification of invasion-metastasis-specific genes may allow us to develop new therapeutic and diagnostic targets for the invasion-metastasis of pancreatic cancer.

| S-EPMC3490402 | biostudies-literature

P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis.

Project description:Gastric cancer (GC) is a common tumor-associated lethal disease, and invasiveness and metastasis are primary challenges in its clinical treatment. Hypoxia microenvironment cannot be ignored in the process of metastasis. Hypoxia inducible factor-1? (HIF-1?) is the core component of the hypoxia signaling pathway. The aim of this study was to identify potential hub genes and signaling pathways associated with HIF-1?. We explored the invasiveness- and metastasis-associated phenotype of GC via bioinformatics analysis and molecular studies. Differentially expressed genes (DEGs) were identified in GC cells and HIF-1?-knockdown GC cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified via centrality analysis and Molecular Complex Detection (MCODE) module analysis. The findings suggested that prolyl 4-hydroxylase beta polypeptide (P4HB) has strong associations with HIF-1?. Further, we observed that HIF-1? and P4HB were upregulated in SGC-7901 and BGC-823 cells. In addition, inhibition of HIF-1? expression reduced invasion and metastasis in GC cells; this effect was partially reversed by P4HB overexpression. Our results confirm that P4HB plays a significant role in the regulatory network of HIF-1?. Therefore, HIF-1? and P4HB may be considered potential biomarkers of GC.

| S-EPMC6699373 | biostudies-literature

A novel FoxM1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis.

Project description:Caveolin-1 (Cav-1), a principal structural component of caveolar membrane domains, contributes to cancer development but its precise functional roles and regulation remain unclear. In this study, we determined the oncogenic function of Cav-1 in preclinical models of pancreatic cancer and in human tissue specimens. Cav-1 expression levels correlated with metastatic potential and epithelial-mesenchymal transition (EMT) in both mouse and human pancreatic cancer cells. Elevated levels in cells promoted EMT, migration, invasion, and metastasis in animal models, whereas RNA interference (RNAi)-mediated knockdown inhibited these processes. We determined that levels of Cav-1 and the Forkhead transcription factor FoxM1 correlated directly in pancreatic cancer cells and tumor tissues. Enforced expression of FoxM1 increased Cav-1 levels, whereas RNAi-mediated knockdown of FoxM1 had the opposite effect. FoxM1 directly bound to the promoter region of Cav-1 gene and positively transactivated its activity. Collectively, our findings defined Cav-1 as an important downstream oncogenic target of FoxM1, suggesting that dysregulated signaling of this novel FoxM1-Cav-1 pathway promotes pancreatic cancer development and progression.

| S-EPMC3271134 | biostudies-literature

Phosphoproteome Analysis of Invasion and Metastasis-Related Factors in Pancreatic Cancer Cells.

Project description:Mechanisms of abnormal protein phosphorylation that regulate cell invasion and metastasis in pancreatic cancer remain obscure. In this study, we used high-throughput phosphorylation array to test two pancreatic cancer cell lines (PC-1 cells with a low, and PC-1.0 cells with a high potential for invasion and metastasis). We noted that a total of 57 proteins revealed a differential expression (fold change ? 2.0). Six candidate proteins were further validated by western blot with results found to be accordance with the array. Of 57 proteins, 32 up-regulated proteins (e.g. CaMK1-? and P90RSK) were mainly involved in ErbB and neurotrophin signaling pathways as determined using DAVID software, while 25 down-regulated proteins (e.g. BID and BRCA1) were closely involved in apoptosis and p53 signaling pathways. Moreover, four proteins (AKT1, Chk2, p53 and P70S6K) with different phosphorylation sites were found, not only among up-regulated, but also among down-regulated proteins. Importantly, specific phosphorylation sites can affect cell biological functions. CentiScaPe software calculated topological characteristics of each node in the protein-protein interaction (PPI) network: we found that AKT1 owns the maximum node degrees and betweenness in the up-regulation protein PPI network (26 nodes, average path length: 1.89, node degrees: 6.62±4.18, betweenness: 22.23±35.72), and p53 in the down-regulation protein PPI network (17 nodes, average path length: 2.04, node degrees: 3.65±2.47, betweenness: 16.59±29.58). In conclusion, the identification of abnormal protein phosphorylation related to invasion and metastasis may allow us to identify new biomarkers in an effort to develop novel therapeutic drug targets for pancreatic cancer treatment.

| S-EPMC4807880 | biostudies-literature

?-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion.

Project description:Recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of PSCs and hypoxia in pancreatic cancer aggressiveness, and examined the potential protective effect of ?-mangostin on hypoxia-driven pancreatic cancer progression. Our data indicate that hypoxic PSCs exploit their oxidative stress due to hypoxia to secrete soluble factors favouring pancreatic cancer invasion. ?-Mangostin suppresses hypoxia-induced PSC activation and pancreatic cancer cell invasion through the inhibition of HIF-1? stabilization and GLI1 expression. Increased generation of hypoxic ROS is responsible for HIF-1? stabilization and GLI1 upregulation. Therefore, ?-mangostin may be beneficial in preventing hypoxia-induced pancreatic cancer progression.

| S-EPMC4005872 | biostudies-literature

Pancreatic Cancer-Derived Exosomes Promote the Proliferation, Invasion, and Metastasis of Pancreatic Cancer by the miR-3960/TFAP2A Axis.

Project description:BackgroundThe microRNAs (miRNAs) in cancer-derived exosomes have the ability to change tumor microenvironment. This study aims to investigate the role of miRNA in cancer-derived exosomes in pancreatic cancer (PC).MethodsBased on the analysis of PC-derived and healthy exosomes by bioinformatics analysis and quantitative real-time PCR validation, the miR-3960 was identified to be the most significantly different miRNA, and TFAP2A proved as its potential target gene. Besides, the exosomes were isolated from PANC-1 cells and identified. After that, PANC-1 cells were treated with the isolated exosomes or transfected with miR-3960 mimics or si-TFAP2A, the effect of PC-derived exosomes, as well as the miR-3960/TFAP2A axis in PC cells, were assessed by the CCK-8, EDU staining, Transwell, cell colony formation, and flow cytometry assays. Furthermore, the effects of exosomes and the miR-3960/TFAP2A axis on PC tumor growth were observed in tumor-bearing mice by the measurement of tumor weight and volume, and hematoxylin-eosin staining. Moreover, the expressions of TFAP2A/PTEN/AKT signaling proteins were detected by Western blot.ResultsPC-derived exosomes were isolated successfully and proved to have promotion effects on the proliferation, metastasis, and invasion of PC cells both in vitro and tumor growth in vivo. Also, the PC-derived exosomes upregulated the TFAP2A, Bcl-2, and p-AKT/AKT protein levels, and inhibited PTEN and Bax levels and PANC-1 cell apoptosis. Overexpression of miR-3960 antagonized the promotion effect of exosomes on PC cells and the TFAP2A/PTEN/AKT signaling pathway, inhibiting the growth of tumors. Besides, si-TFAP2A enhanced the inhibitory effect of miR-3960 in PC.ConclusionMiR-3960 antagonizes the promotion effect of tumor-derived exosomes on the proliferation, invasion, and metastasis of PC via suppressing TFAP2A.

| S-EPMC9588341 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data