Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Blocking the Angiopoietin-2-dependent Integrin beta-1 signaling axis abrogates small cell lung cancer invasion and metastasis

ABSTRACT: Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive. We used an autochthonous SCLC mouse model and matched primary and metastatic SCLC patient samples to investigate the molecular characteristics of tumor metastasis. We demonstrate that tumor cell invasion and liver metastasis in SCLC are triggered by an Angiopoietin-2/Integrin beta-1-dependent pathway in tumor cells, mediated by focal adhesion kinase-Src kinase signaling. Strikingly, CRISPR-Cas9 knock out of Integrin beta-1 or blocking Integrin beta-1 signaling by an anti-Angiopoietin-2 treatment abrogates liver metastasis formation in vivo. Interestingly, analysis of a unique collection of matched primary and metastatic SCLC patient samples confirmed a strong increase of Integrin beta-1 in liver metastasis in comparison to the primary tumor. We further show that Angiopoietin-2 blockade combined with anti-VEGFR and PD-1-targeted treatment displays synergistic treatment effects in SCLC. Together, our data demonstrate a fundamental role of Angiopoietin-2/Integrin beta-1 signaling in SCLC cells for tumor cell invasion and liver metastasis and provide a new effective treatment strategy for patients with SCLC.

ORGANISM(S): Mus musculus

PROVIDER: GSE262409 | GEO | 2024/03/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CdGAP is a Talin-binding protein and a target of TGF-β signaling that promotes HER2-positive breast cancer growth and metastasis

Project description:Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. We show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2+) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites. CdGAP depletion in HER2+ murine primary tumors mediates crosstalk with a Dlc1-RhoA pathway and is associated with a transforming growth factor-β (TGF-β)-induced EMT transcriptional signature. To further delineate the molecular mechanisms underlying the pro-migratory role of CdGAP in breast cancer cells, we searched for CdGAP interactors by performing a proteomic analysis using HEK293 cells overexpressing GFP-CdGAP. We found that CdGAP interacts with the adaptor Talin to modulate focal adhesion dynamics and integrin activation. Moreover, HER2+ breast cancer patients with high CdGAP mRNA expression combined with a high TGF-β-EMT signature are more likely to present lymph node invasion. Our results suggest CdGAP as a candidate therapeutic target for HER2+ metastatic breast cancer by inhibiting TGF-β and Integrin/Talin signaling pathways.

2023-07-14 | PXD043376 | Pride

Marine bacterial polysaccharide EPS11 inhibits metastasis and invasion of liver cancer cells by directly targeting type I collagen

Project description:Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for approximately 90%, and it has a ﬁve-year survival rate around only 30–40%. Similar to other kinds of cancers, tumor metastasis remains the primary cause of mortality of HCC patients. It is well known that metastasis is a multistage process that requires cancer cell detachment from the primary tumor, survival in the circulation, settlement at distant sites and growth. During this process, metastatic cells go through detachment, migration, invasion and adhesion, and inhibition of any one of these steps has the potential to block the entire metastatic process. However, there is very little advancement in the area of blocking tumor metastasis, therefore, new effective agents possessing anti-metastasis activities are urgently needed for better prevention and treatment of HCC and other cancers. Our previous results suggested that EPS11, a novel marine bacterial polysaccharide, might be a potential drug candidate for human non-small cell lung carcinoma treatment. In this study, we further investigate the anticancer mechanisms against liver cancer and the anti-metastatic effects of EPS11.

2022-02-17 | PXD025155 | Pride

Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [HNRNPK_OE]

Project description:The survival rate of colorectal liver metastases remains low. Long noncoding lncRNAs is emerging as a novel class of master regulators of cell invasion and metastasis. In this study, analysis of the lncRNA expression dynamics in the colorectal liver metastases, primary colorectal tumor and normal tissues led to the identification of the metastasis-specific expression of a set of lncRNAs including CRLM1. CRLM1 inhibited apoptosis and promoted metastasis and invasion of colorectal cancer cells, and also promoted tumor growth in nude mice. CRLM1 weakly associated with chromatin regions of genes involved in cell adhesion and DNA damage, correlated with CRLM1-regulated gene expression bidirectionally. CRLM1 physically interacts with and promotes the nuclear localization of the metastasis protein hnRNPK. CRLM1 effectively promotes hnRNPK promoter occupancy, and co-regulate gene expression. These findings suggest a potential biomarker and druggable target for treatment of colorectal liver metastases.

2022-08-03 | GSE168147 | GEO

Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [HNRNPK_CHIP]

2022-08-03 | GSE168146 | GEO

Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [CRLM1_OE]

2022-08-03 | GSE168145 | GEO

Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [CRLM1_CHIRP]

2022-08-03 | GSE168144 | GEO

A macrophage autonomous alpha4beta1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, M-NM-14M-NM-21 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. Bone marrow derived macrophages from five wild type and five Rac2 -/- mutant C57BL mice.

2012-10-02 | E-GEOD-41236 | biostudies-arrayexpress

A macrophage autonomous Î±4Î²1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, Î±4Î²1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis. SmoA1 Tg MB tumor cells were sorted into CD15+ and CD15- populations. RNA from these samples were hybridized to Affymetrix Mouse Genome 1.0 ST array.

2012-11-15 | E-GEOD-41717 | biostudies-arrayexpress

Dose-dependent dual roles of PDGF-BB–PDGFR-β in vascular remodeling and opposing effects of anti-PDGF drug-induced metastasis

Project description:Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR-β signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-β. Inactivation of the PDGFR-β signaling system led to decreased levels of integrin α1β1, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis.

2013-07-22 | GSE46564 | GEO

A macrophage autonomous α4β1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth and metastasis

Project description:Macrophages, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. The signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. We have discovered an ECM dependent signaling pathway in macrophages that regulates M2 macrophage differentiation, tumor growth, invasion and metastasis. We provide direct evidence that a macrophage autonomous, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110 isoform (PTEN-PI-3 kinase pathway) to control metastasis.

2012-11-15 | GSE41717 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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