The Role of Notch1 Signaling in Anaplastic Thyroid Carcinoma

Abstract

PurposeThe Notch signaling pathway is widely expressed in normal, reactive, and neoplastic tissues; however, its role in thyroid tissues has not been fully elucidated. Therefore, this study was conducted to characterize the expression of the Notch signaling pathway in papillary thyroid cancer (PTC) cells and anaplastic thyroid cancer (ATC) cells.Materials and MethodsExpression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA techniquewas employed to knock down Notch1 expression in ATC and PTC cell lines.ResultsThe expression of activated Notch1 was higher in ATC cases than in PTC cases. Inhibition of Notch1 significantly reduced proliferation and migration of ATC cells, but not PTC cells. In addition, inhibition of Notch1 in ATC cells significantly reduced the expression of key markers of epithelial-mesenchymal transition and cancer stem cells. Conversely, changes in the expression of these proteins were not observed in PTC cells.ConclusionThe results of this study suggest that Notch1 expression plays different roles in tumor progression in ATC and PTC cells. We also found that Notch1 expression was significantly related to the highly invasive or proliferative activity of ATC cells.

Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma

“…By contrast, Kim et al . reported that the expression of activated NOTCH1 was higher in ATCs than in PTCs indicating a role of this pathway in aggressive evolution of thyroid cancer (19). According to these authors, inhibition of NOTCH1 significantly reduced proliferation and migration of ATC cells, but not PTC cells.…”

“…Noticeably, Kim et al . postulated that NOTCH signaling influences the malignant potential of thyroid cancer and observed a NOTCH1-dependent reduction of epithelial-mesenchymal transition (EMT) and cancer stem cells markers in anaplastic tumors (19). In parallel, the expression of NOTCH1 receptor seems to be related to tumor invasiveness in PTC, and it has been proposed as molecular marker of poor prognosis (20, 21).…”

Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy

“…Interestingly, Kim et al demonstrated that the activated Notch-1 expression was higher in cases of ATC than in cases of PTC. Inhibiting Notch-1 significantly reduced the proliferation and migration of ATC cells, but not that of PTC cells [ 150 ]. In addition, inhibiting Notch-1 in ATC cells drastically reduced the expression of key markers representing epithelial to mesenchymal transition and cancer cell stemness.…”

“…In addition, inhibiting Notch-1 in ATC cells drastically reduced the expression of key markers representing epithelial to mesenchymal transition and cancer cell stemness. Conversely, changes in the expression of these markers were not observed in PTC cells when the Notch-1 inhibition was applied [ 150 ]. This study demonstrated the different roles of Notch-1 expression in cancer cell aggressiveness between ATC and PTC, suggesting the heterogeneity of CSCs in thyroid cancer.…”

Effect of miR‑449a‑mediated Notch signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells

“…and survival of normal cells or cancer cells in various cases. Notch signaling transduction consists of four Notch receptors (Notch 1, 2, 3 and 4) and five ligands [Delta 1, 3, 4 and Jagged (Jag) 1 and 2] (8). The Notch signaling pathway has been revealed to contribute to the progression of several cancers, including the proliferation, invasion and apoptosis of cancer cells (9,10).…”