Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Annexin A2 controls pancreatic cancer invasion and metastasis through a novel axon guidance pathway

ABSTRACT: The mechanisms involved in promoting metastasis of pancreatic ductal adenocarcinoma have yet to be elucidated. Here, we show that AnnexinA2 regulates the secretion of Semaphorin3D from pancreatic tumor cells allowing it to bind to its receptor PlexinD1 on the surface of the tumor cell, which induces invasion and metastasis. Knockdown of AnnexinA2 or Semaphorin3D decreases the metastatic potential of pancreatic tumor cells, while over expression of AnnexinA2 or Semaphorin3D is sufficient to rescue the invasion capacity of these cells. Clinically, we found that Semaphorin3D expression correlates with poor survival and increased metastatic potential in human PDA patients. This study identified a novel axon guidance pathway downstream of AnnexinA2 that can be targeted in the treatment of metastatic pancreatic cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE62285 | GEO | 2015/09/03

SECONDARY ACCESSION(S): PRJNA263743

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Annexin A2 controls pancreatic cancer invasion and metastasis through a novel axon guidance pathway

Project description:The mechanisms involved in promoting metastasis of pancreatic ductal adenocarcinoma have yet to be elucidated. Here, we show that AnnexinA2 regulates the secretion of Semaphorin3D from pancreatic tumor cells allowing it to bind to its receptor PlexinD1 on the surface of the tumor cell, which induces invasion and metastasis. Knockdown of AnnexinA2 or Semaphorin3D decreases the metastatic potential of pancreatic tumor cells, while over expression of AnnexinA2 or Semaphorin3D is sufficient to rescue the invasion capacity of these cells. Clinically, we found that Semaphorin3D expression correlates with poor survival and increased metastatic potential in human PDA patients. This study identified a novel axon guidance pathway downstream of AnnexinA2 that can be targeted in the treatment of metastatic pancreatic cancer. Two primary pancreatic tumor cell lines were analyzed. The first primary line was derived from a KrasG12D/p53172H/Pdx-1Cre mouse, which served as the reference sample. The second primary line was derived from a KrasG12D/p53R172H/Pdx-1Cre/AnxA2-/- mouse.

2015-09-03 | E-GEOD-62285 | biostudies-arrayexpress

Enhancer reprogramming promotes pancreatic cancer progression and metastasis [RNA-seq]

Project description:Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during each stage of PDA progression. This approach revealed that the metastatic transition is accompanied by massive, and recurrent alterations in enhancer activity. We implicate the transcription factors FOXA1 and GATA5 as drivers of enhancer activation in this system, a mechanism that we show renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. FOXA1 and GATA5 were found to activate a foregut endoderm transcriptional program in PDA cells, without altering genes associated with the epithelial-to- mesenchymal transition. Collectively, our study implicates FOXA1/GATA5 upregulation, enhancer reprogramming, and a novel retrograde developmental transition in PDA progression and metastasis.

2017-07-31 | GSE99310 | GEO

Enhancer reprogramming promotes pancreatic cancer progression and metastasis [ChIP-seq]

2017-07-31 | GSE99284 | GEO

Enhancer reprogramming promotes pancreatic cancer progression and metastasis [ATAC-seq]

2017-07-31 | GSE99275 | GEO

Transcriptional profiling of autophagy proficient and compromised cell lines, determined by expression levels of Atg5

Project description:Autophagy is activated in pancreatic ductal adenocarcinoma (PDAC) and is currently being considered a promising therapeutic target in clinical trials. PDAC is a highly lethal disease with incidence rate equalling mortality rate. Main reasons for PDAC lethality are late-stage diagnosis, high agressiveness and metastatic rate, lack of effective treatments as well as specific diagnostic markers. Here we show that varying levels of the Autophagy related gene 5 (Atg5) determine pancreatic tumor formation and malignancy. While homozygous deletion of Atg5 blocks tumor progression in an in vivo model of PDAC, heterozygous deletion increases tumor aggressiveness and metastasis. Further analyses reveal that monoallelic loss of Atg5 affects mitochondrial homeostasis, changes intracellular calcium oscillations, heightens extracellular cathepsin activities , and promotes a pro-tumorigenic inflammatory microenvironment collectively enhancing tumor cell migration, invasion, and metastasis. Future treatments should take into account that variations in the autophagy pathway may have opposing effects on pancreatic tumor load, especially considering the multitude of autophagy inhibitors currently tested in clinical trials.

2018-10-15 | E-MTAB-6275 | biostudies-arrayexpress

Rhodes2019 - Immune-Mediated theory of Metastasis

Project description:Abstract: Accumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system - as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example - have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed "immune-mediated" theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti- and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor "education" of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the pro-tumor effects of the immune system in metastatic cancer.

2024-09-02 | BIOMD0000000926 | BioModels

Pancreatic cancer xenograft tumor RNA sequencing and pathologic differentiation of matched human tumors.

Project description:Epithelial to mesenchymal transition (EMT) in pancreatic cancer is believed to correlate with metastatic probability and aggressiveness. In the clinical setting, tumor staging and grading reflect tumor aggressiveness, tumor invasion, and gross metastasis and are used to guide treatment options. These data were analyzed to correlate commonly used laboratory RNA sequencing analysis with clinically defined differentiation status. This dataset provides evidence that mesenchymal genes are enriched in xenograft tumors from poorly differentiated human tumors.

2024-01-15 | GSE252909 | GEO

S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells [HG-U133B]

Project description:Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling We have performed microarray gene expression analysis of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver and pancreatic liver metastases to identify potential therapeutic targets.

2013-08-15 | E-GEOD-19280 | biostudies-arrayexpress

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (ChIP-seq)

Project description:Lineage plasticity is a prominent feature of pancreatic ductal adenocarcinoma (PDA) cells, which can occur via deregulation of lineage-specifying transcription factors. Here, we show that the zinc finger protein ZBED2 is aberrantly expressed in PDA and regulates tumor cell identity in this disease. Unexpectedly, our epigenomic experiments reveal that ZBED2 is a sequence-specific transcriptional repressor of interferon-stimulated genes, which occurs through antagonism of Interferon Regulatory Factor 1 (IRF1)-mediated transcriptional activation at co-occupied promoter elements. Consequently, ZBED2 attenuates the transcriptional output and growth arrest phenotypes downstream of interferon signaling in multiple PDA cell line models. We also found that ZBED2 is preferentially expressed in the squamous molecular subtype of human PDA, in association with inferior patient survival outcomes. Consistent with this observation, we show that ZBED2 can repress the pancreatic progenitor transcriptional program, enhance motility, and promote invasion in PDA cells. Collectively, our findings suggest that high ZBED2 expression is acquired during PDA progression to suppress the interferon response pathway and to promote lineage plasticity in this disease.

2020-05-09 | GSE141606 | GEO

ZBED2 is an antagonist of Interferon Regulatory Factor 1 and modifies cell identity in pancreatic cancer (RNA-seq)

2020-05-09 | GSE141605 | GEO