Thyroid cancer

Pathway ID: SIGNOR-TCView in NDEx

Description: Thyroid cancer (TC) is the most common tumor of the endocrine system. The most frequent type of TC is papillary thyroid cancer (PTC), comprising 90% of all cases. The second most common type is follicular thyroid cancer (FTC) that accounts for 10% of total. PTCs and FTCs both arise from the thyroid follicular cells and are termed differentiated thyroid cancer (DTC). Medullary thyroid cancer (MTC) instead arises from the parafollicular C cells and represents 5% of all TCs. Finally, anaplastic thyroid cancer is one of the most aggressive TCs and can arise from DTCs that dedifferentiate or it can develop de-novo. Ionizing radiation is the only exogenous factor which has been identified as causing TC, mostly the papillary form. PCs frequently have genetic alterations leading to the activation of the MAPK signaling pathway like point mutations of the BRAF and RAS genes and RET/PTC rearrangement. BRAFV600E results in the constitutive activation of this serine/threonine kinase and occurs in approximately 45% of PTCs. Gene translocations resulting in oncogenic rearrangements in PC are best exemplified by more than 10 types of RET–PTC translocations resulting in oncoproteins that activate the MAPK and PI3K–AKT pathways. Most frequent alterations in FC include RAS mutations and PAX8-PARγ rearrangement. Point mutations of RET receptor are crucial for the development of medullary carcinomas. Many of these mutations, particularly those involved in the activation of the MAPK pathway, are being explored as therapeutic targets for thyroid cancer.

Curated by: Marta Iannuccelli

complexity level

level 1 seed interactions
level 2 connect
level 3 first neighbors
level 4 all
level 5 PPI

27 Seed Entities

Name Primary ID
KRAS P01116
SHC1 P29353
MYC P01106
BRAF P15056
Proliferation SIGNOR-PH4
TGFBR1 P36897
GRB2 P62993
Ionizing radiation SIGNOR-ST16
ELE1-RET Q99931
PTEN P60484
TGFB1 P01137
Apoptosis SIGNOR-PH2
SLC5A5 Q92911
FOXO3 O43524
Cell Cycle Block SIGNOR-PH10
RET P07949
SOS1 Q07889
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate CHEBI:16618
CTNNB1 P35222
PPARG P37231
PDPK1 O15530
SMAD3 P84022
Survival SIGNOR-PH13