Amplification and Expansion of Oncogenic Pathways as Metastatic Traits (Homo sapiens)

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1Receptor Tyrosine KinasesCell survivalTCFsMetastatic traits acquired by a quantitative gain in pathway outputStemnessGPCRChemotaxisTumorigenesisSurvivalHistone H3K27 demethylationMetastatic traits acquired by a qualitative expansion of pathway outputVHLCYTIPVEGFATNCTCF7WntJAGGEDPeriostinVCAM1PI3KCXCR4SRCNOTCHHIF2API3KCell survivalTCF7L1TCF7L2LEF1DNAdemethylation


Description

This pathway is based on Figure 4 of "Origins of metastatic traits."(See Bibliography).The majority of cancer cells released from tumors die off, so cancer biologists are trying to figure out exactly what gives certain cells the ability to colonize other distant organs. Specific genes and mediators of metastasis have been identified, but it remains mostly unknown how cancer cells acquire these traits.

Metastatic traits acquired by a quantitative gain in pathway output: These pathways demonstrate metastatic traits acquired by a quantitative gain in pathway output. The PI3K-Akt signaling pathway, which is augmented by VCAM-1 and SRC, leads to increased cell survival, a significant metastatic trait. Similarly, TCF augments the output of the NOTCH and, along with periostin, Wnt signaling pathways. As the signaling of these pathways increases, the metastatic and oncogenic potential of the cell also increase.

Metastatic traits acquired by a qualitative expansion of pathway output: This pathway demonstrates metastatic traits acquired by a qualitative expansion of pathway output. Loss of the von Hippel-Lindau tumor suppressor (VHL) in renal cell carcinoma leads to increased activation of hypoxia-inducible transcription factors (HIFs). Histone H3K27 and CYTIP give the VHL-HIF pathway access to new target genes. Each of these new target genes, in this case CXCR4, VEGFA, and CYTIP, lead to an increase in a metastatic trait. Here, the level of metastatic fitness is not linearly proportional to pathway activity; rather, the pathway activates an additional set of factors that affect metastatic fitness.

Quality Tags

Ontology Terms

 

Bibliography

  1. Vanharanta S, Massagué J; ''Origins of metastatic traits.''; Cancer Cell, 2013 PubMed

History

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CompareRevisionActionTimeUserComment
90110view18:59, 13 October 2016KhanspersModified description
90109view18:59, 13 October 2016KhanspersModified title
90108view18:58, 13 October 2016Khansperslayout changes etc
88755view18:45, 14 August 2016AAR&CoOntology Term : 'von Hippel-Lindau disease' added !
88754view18:43, 14 August 2016AAR&CoOntology Term : 'cancer pathway' added !
88547view01:32, 11 August 2016AAR&CoModify Datanode
88546view01:30, 11 August 2016AAR&CoModify Datanodes
88545view01:20, 11 August 2016AAR&CoModified description
88543view01:14, 11 August 2016AAR&CoAdd citation
88003view13:27, 25 July 2016ElisaOntology Term : 'disease pathway' added !
86272view12:49, 9 July 2016AAR&CoChange of Title
86136view13:16, 1 July 2016AAR&CoModified description
86135view13:15, 1 July 2016AAR&CoNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CXCR4GeneProductENSG00000121966 (Ensembl)
CYTIPGeneProductENSG00000115165 (Ensembl)
HIF2AGeneProductENSG00000116016 (Ensembl)
JAGGEDGeneProductENSG00000101384 (Ensembl)
LEF1GeneProductENSG00000138795 (Ensembl)
NOTCHGeneProductENSG00000148400 (Ensembl)
PI3KGeneProductENSG00000105851 (Ensembl)
PeriostinGeneProductENSG00000133110 (Ensembl)
SRCGeneProductENSG00000197122 (Ensembl)
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProductENSG00000152284 (Ensembl)
TCF7L2GeneProductENSG00000148737 (Ensembl)
TNCGeneProductENSG00000041982 (Ensembl)
VCAM1GeneProductENSG00000162692 (Ensembl)
VEGFAGeneProductENSG00000112715 (Ensembl)
VHLGeneProductENSG00000134086 (Ensembl)
WntGeneProductP09544 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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