Fig. 2:

The effect of tumor suppressor genes during suppression of pathways involved in thyroid cancer tumorigenesis and progress (Source: The authors of this paper).

SLC5A8 and TSHR inhibit the RAF/MEK/ERK pathway, involved cell cycle through cyclin D1 and angiogenesis.

RASSF1 acts through three ways. First, inhibiting the RAS oncogene and consequently preventing RAF/MEK/ERK pathway, cell cycle and angiogenesis. Second, motivating pro-apoptotic kinases (MSTs) and then inducing apoptosis. Third, activating c-Jun N-terminal kinase (JNK) pathway and then stopping cell cycle through cyclin D1.

RUNX3 interrupts Wnt/β-catenin signaling pathway, involved in cell proliferation and invasion. It also forms the complex with TCF4-b-catenin complex and consequently inhibiting the cyclinD1 activity. RUNX3 cooperates to activating the Transforming growth factor-β (TGF-β) pathway by induction of p21 and Bim and regulates apoptosis. RARβ forms complex with RARα and induced apoptosis and inhibit cell cycle.

P16 forms complex with Cyclin-dependent kinase 4 (CDK4) and then inhibits cyclin D1, prevents cell growth and stop cell cycle.

PTEN interrupts in the phosphoinositol 3-kinase (PI3K) AKT pathway through effects on common genetic alterations in this pathway, which plays an important role in tumorigenesis of thyroid cancer.

DAPK1 inhibit the RAF/MEK/ERK pathway, involved cell cycle and angiogenesis through Mitogen- and stress-activated kinase 1 (MSK1). In addition,

TIMP3 inhibits angiogenesis through effects on Vascular endothelial growth factor (VEGF) signaling and matrix metallopeptidase 9 (MMPs)