TGF-beta signaling in thyroid cells for epithelial-mesenchymal transition (WP3859)

Homo sapiens

This pathway is based on the Figure 7 of "Cadherin 6 Is a New RUNX2 Target in TGF-β Signalling Pathway" (see bibliography). TGF-B is a target gene in thyroid cells in the causation of cancer. When TGF-B is activated, the pathway can take 2 directions, through a SMAD pathway or a Non-Smad pathway. Through the SMAD pathway, SMAD separates into SMAD2/3, SMAD4, and involves phosphates into the nuclear signalling. Through the Non-SMAD pathway, the activation of MAPK and Pi3k causes the activation of ERK, AKT and phosphates, and then into the nuclear signalling. Within the nuclear signalling, EMT-TF has two responses, early and late. With the early response, EMT-TF signals to Id1 and RUNX2, and with the late response, EMT-TF signals to Snai1 and Snai2. Depending on the response also dictates the type of marker that will follow. If early, N-CAD,FN1,VIM,TNC, and CDH6 all cause the activation of the Mesenchymal markers. If late, E-CAD, and CDH16 cause the inhibition of the Epithelial Markers. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


AAR&Co , Martina Summer-Kutmon , Egon Willighagen , Kristina Hanspers , and Eric Weitz


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Homo sapiens




Disease Ontology

thyroid gland cancer

Pathway Ontology

signaling pathway


Label Type Compact URI Comment
RUNX2 GeneProduct ensembl:ENSG00000124813
PI3K GeneProduct uniprot:P91634
CDH16 GeneProduct ensembl:ENSG00000166589
E-CAD GeneProduct uniprot:P12830
TNC GeneProduct ensembl:ENSG00000041982
ERK GeneProduct uniprot:P27361 ERK Not Specified
SMAD3 GeneProduct ensembl:ENSG00000166949
SMAD4 GeneProduct ensembl:ENSG00000141646
ID1 GeneProduct ensembl:ENSG00000125968
MAPK GeneProduct ensembl:ENSG00000100030 MAPK Not Specified
FN1 GeneProduct ensembl:ENSG00000115414
SNAI1 GeneProduct ensembl:ENSG00000124216
CDH6 GeneProduct ensembl:ENSG00000113361
VIM GeneProduct ensembl:ENSG00000026025
SMAD2 GeneProduct ensembl:ENSG00000175387
TGF-B GeneProduct uniprot:P01137
SNAI2 GeneProduct ensembl:ENSG00000019549
AKT GeneProduct ensembl:ENSG00000142208 AKT Not Specified
N-CAD Protein uniprot:A0A024RC42


  1. Cadherin 6 is a new RUNX2 target in TGF-β signalling pathway. Sancisi V, Gandolfi G, Ragazzi M, Nicoli D, Tamagnini I, Piana S, et al. PLoS One. 2013 Sep 12;8(9):e75489. PubMed Europe PMC Scholia