Amplification and expansion of oncogenic pathways as metastatic traits (Homo sapiens)

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Cell survivalstemnessSurvivalABTumorigenesisChemotaxisVCAM1Histone H3K27 demethylationTCFCXCR4SRCPI3KAKT1NOTCHHIF2AVHLTNCCXCR4PeriostinWntJAGGEDCXCL12CYTIPDNA demethylationIGF1recIGF1VEGFARTKPI3KAKT1Cell survival


Description

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.

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Bibliography

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

History

View all...
CompareRevisionActionTimeUserComment
128581view23:21, 14 February 2024EweitzEconomize layout
117647view11:42, 22 May 2021EweitzModified title
108162view10:45, 29 November 2019FehrhartOntology Term : 'cancer' added !
105879view04:51, 16 August 2019KhanspersModified description
105526view05:59, 9 August 2019KhanspersModified description
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

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
CXCL12GeneProductENSG00000107562 (Ensembl)
CXCR4GeneProductENSG00000121966 (Ensembl)
CYTIPGeneProductENSG00000115165 (Ensembl)
DNA demethylationGeneProduct
HIF2AGeneProductENSG00000116016 (Ensembl)
Histone H3K27 demethylation
IGF1GeneProductENSG00000017427 (Ensembl)
IGF1rec GeneProductENSG00000140443 (Ensembl)
JAGGEDGeneProductENSG00000101384 (Ensembl)
NOTCHGeneProductENSG00000148400 (Ensembl)
PI3KGeneProductENSG00000105851 (Ensembl)
PeriostinGeneProductENSG00000133110 (Ensembl)
RTK GeneProductreceptor tyrosine kinase
SRCGeneProductENSG00000197122 (Ensembl)
TCFGeneProduct
TNCGeneProductENSG00000041982 (Ensembl)
VCAM1GeneProductENSG00000162692 (Ensembl)
VEGFAGeneProductENSG00000112715 (Ensembl)
VHLGeneProductENSG00000134086 (Ensembl)
WntGeneProduct

Annotated Interactions

No annotated interactions

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