Amplification and expansion of oncogenic pathways as metastatic traits (Homo sapiens)
From WikiPathways
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.
Pathway A: 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.
Pathway B: 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
- Vanharanta S, Massagué J; ''Origins of metastatic traits.''; Cancer Cell, 2013 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
AKT1 | GeneProduct | ENSG00000142208 (Ensembl) | |
CXCL12 | GeneProduct | ENSG00000107562 (Ensembl) | |
CXCR4 | GeneProduct | ENSG00000121966 (Ensembl) | |
CYTIP | GeneProduct | ENSG00000115165 (Ensembl) | |
DNA demethylation | GeneProduct | Q13686 (Uniprot-TrEMBL) | |
HIF2A | GeneProduct | ENSG00000116016 (Ensembl) | |
Histone H3K27 demethylation | GeneProduct | ENSG00000147050 (Ensembl) | |
IGF1 | GeneProduct | ENSG00000017427 (Ensembl) | |
IGF1rec | GeneProduct | ENSG00000140443 (Ensembl) | |
JAGGED | GeneProduct | ENSG00000101384 (Ensembl) | |
NOTCH | GeneProduct | ENSG00000148400 (Ensembl) | |
PI3K | GeneProduct | ENSG00000105851 (Ensembl) | |
Periostin | GeneProduct | ENSG00000133110 (Ensembl) | |
RTK | GeneProduct | P04626 (Uniprot-TrEMBL) | receptor tyrosine kinase |
SRC | GeneProduct | ENSG00000197122 (Ensembl) | |
TCF | GeneProduct | P15884 (Uniprot-TrEMBL) | |
TNC | GeneProduct | ENSG00000041982 (Ensembl) | |
VCAM1 | GeneProduct | ENSG00000162692 (Ensembl) | |
VEGFA | GeneProduct | ENSG00000112715 (Ensembl) | |
VHL | GeneProduct | ENSG00000134086 (Ensembl) | |
Wnt | GeneProduct | P09544 (Uniprot-TrEMBL) |
Annotated Interactions
No annotated interactions