Altogether, our findings provide insight into the role of SOSTDC1 as a novel functional tumor suppressor in follicular thyroid cancer through modulating the activities of PI3K/Akt and MAPK/Erk signaling pathways.
These results provide in vivo evidence for CD147 upregulation in FTC and in vitro evidence for EGF-stimulated CD147 induction via the PI3K, ERK, and JNK pathways.
It is proposed that genetic alterations in the PI3K/Akt pathway promote thyroid cell transformation to FTC and that genetic alterations in the MAPK pathway promote cell transformation to PTC; accumulation of multiple genetic alterations that can activate both pathways promotes thyroid cancer aggressiveness and progression to ATC.
Mice with overactivation of the phosphatidylinol-3-kinase (PI3K)-AKT and/or thyrotropin-regulated signaling pathways have been found to develop follicular thyroid cancer.
Genetic alterations in the RTKs and PI3K/Akt and MAPK pathways are extremely prevalent in ATC and FTC, providing a strong genetic basis for an extensive role of these signaling pathways and the development of therapies targeting these pathways for ATC and FTC, particularly the former.
APP regulation was studied in vitro in differentiated (FRTL-5) and dedifferentiated follicular thyroid carcinomas (FTC-133) thyroid cells after specific inhibition or activation of the cAMP-PKA, the PI3K/AKT or the protein kinase c (PKC) cascades.
The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate.
These data from a Chinese cohort provide further genetic evidence suggesting that dysregulated PI3K/Akt pathway plays a significant role in the pathogenesis of thyroid tumors, particularly FTC.
Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC).