Dataset Information

MAPK, NF?B, and VEGF signaling pathways regulate breast cancer liver metastasis.

ABSTRACT: In this study, we investigated the molecular pathways regulating breast cancer liver metastasis. We identified 48 differentially expressed genes (4 upregulated and 44 downregulated) by analyzing microarray dataset GSE62598 from Gene Expression Omnibus (GEO). We constructed a genetic interaction network with 84 nodes and 237 edges using the String consortium database. The network was reliably robust with a clustering coefficient (cc) of 0.598 and protein-protein interaction (PPI) enrichment p value of zero. Using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, we identified MAPK, NF?B and VEGF signaling pathways as the most critical pathways regulating breast cancer liver metastasis. These results indicate that the distinct breast cancer metastatic stages, including dissemination from the primary breast tumor, transit through the vasculature, and survival and proliferation in the liver, are regulated by the MAPK, NF?B, and VEGF signaling pathways.

SUBMITTER: Chen X

PROVIDER: S-EPMC5731887 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MAPK, NFκB, and VEGF signaling pathways regulate breast cancer liver metastasis.

Chen Xinhua X Zheng Zhihong Z Chen Limin L Zheng Hongyu H

Oncotarget 20170912 60

In this study, we investigated the molecular pathways regulating breast cancer liver metastasis. We identified 48 differentially expressed genes (4 upregulated and 44 downregulated) by analyzing microarray dataset GSE62598 from Gene Expression Omnibus (GEO). We constructed a genetic interaction network with 84 nodes and 237 edges using the String consortium database. The network was reliably robust with a clustering coefficient (cc) of 0.598 and protein-protein interaction (PPI) enrichment <i>p< ...[more]

PMID: 29254177

Similar Datasets

Project description:BackgroundPatients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear.MethodsVenny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan-Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo.ResultsAccording to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis.ConclusionsThis study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.

Dataset Information

MAPK, NF?B, and VEGF signaling pathways regulate breast cancer liver metastasis.

Publications

MAPK, NFκB, and VEGF signaling pathways regulate breast cancer liver metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets