Amplification and expansion of oncogenic pathways as metastatic traits (WP3678)

Homo sapiens

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. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


AAR&Co , Elisa Cirillo , Kristina Hanspers , Friederike Ehrhart , and Eric Weitz


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Homo sapiens



Disease Ontology

von Hippel-Lindau disease cancer

Pathway Ontology

disease pathway cancer pathway


Label Type Compact URI Comment
VCAM1 GeneProduct ensembl:ENSG00000162692
SRC GeneProduct ensembl:ENSG00000197122
Periostin GeneProduct ensembl:ENSG00000133110
VHL GeneProduct ensembl:ENSG00000134086
VEGFA GeneProduct ensembl:ENSG00000112715
CYTIP GeneProduct ensembl:ENSG00000115165
JAGGED GeneProduct ensembl:ENSG00000101384
PI3K GeneProduct ensembl:ENSG00000105851
TCF7 GeneProduct ensembl:ENSG00000081059
TNC GeneProduct ensembl:ENSG00000041982
NOTCH GeneProduct ensembl:ENSG00000148400
CXCR4 GeneProduct ensembl:ENSG00000121966
Wnt GeneProduct uniprot:P09544
HIF2A GeneProduct ensembl:ENSG00000116016
PI3K GeneProduct ensembl:ENSG00000105851
TCF7L1 GeneProduct ensembl:ENSG00000152284
TCF7L2 GeneProduct ensembl:ENSG00000148737
LEF1 GeneProduct ensembl:ENSG00000138795


  1. Origins of metastatic traits. Vanharanta S, Massagué J. Cancer Cell. 2013 Oct 14;24(4):410–21. PubMed Europe PMC Scholia