The Role of Notch1 Signaling in Anaplastic Thyroid Carcinoma
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Purpose The 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 Methods Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA technique was employed to knock down Notch1 expression in ATC and PTC cell lines. Results The 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. Conclusion The 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.
Abstract
Purpose The 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 Methods Expression of activated Notch1 in ATC and PTC paraffin-embedded tissues was determined by immunohistochemistry. The small interfering RNA technique was employed to knock down Notch1 expression in ATC and PTC cell lines. Results The 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. Conclusion The 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.
참고문헌 (30)
- Jemal A, "Cancer statistics, 2010", CA Cancer J Clin, 60, pp.277~300 (2010)
- Nikiforov YE, "Thyroid carcinoma: molecular pathways and therapeutic targets", Mod Pathol, 21(Suppl 2), pp.S37~S43 (2008)
- Neff RL, "Anaplastic thyroid cancer", Endocrinol Metab Clin North Am, 37, pp.525~538 (2008)
- Pasieka JL, "Anaplastic thyroid cancer", Curr Opin Oncol, 15, pp.78~83 (2003)
- Smallridge RC, "Anaplastic thyroid carcinoma : pathogenesis and emerging therapies", Clin Oncol(R Coll Radiol), 22, pp.486~497 (2010)
- Maillard I, "Notch and cancer : best to avoid the ups and downs", Cancer Cell, 3, pp.203~205 (2003)
- Yoon K, "Notch signaling in the mammalian central nervous system : insights from mouse mutants", Nat Neurosci, 8, pp.709~715 (2005)
- Kopan R, "The canonical Notch signaling pathway : unfolding the activation mechanism", Cell, 137, pp.216~233 (2009)
- Wilson A, "Multiple functions of Notch signaling in self-renewing organs and cancer", FEBS Lett, 580, pp.2860~2868 (2006)
- Bray SJ, "Notch signalling : a simple pathway becomes complex", Nat Rev Mol Cell Biol, 7, pp.678~689 (2006)
- Kanwar R, "Notch signaling: a different sort makes the cut", Curr Biol, 14, pp.R1043~R1045 (2004)
- Fortini ME, "Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling", Nat Rev Mol Cell Biol, 3, pp.673~684 (2002)
- van Es JH, "Notch", gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells, 2005, pp.435, 959~963
- Cao YW, "Implications of the Notch1-Snail", Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma, 2015, pp.31, 70~76
- Gopalakrishnan N, "Synergistic association of Notch and NFkappaB signaling and role of Notch signaling in modulating epithelial to mesenchymal transition in colorectal adenocarcinoma", Biochimie, 107(Pt B), pp.310~318 (2014)
- Stylianou S, "Aberrant activation of notch signaling in human breast cancer", Cancer Res, 66, pp.1517~1525 (2006)
- Wang Z, "The role of Notch signaling pathway in epithelial-mesenchymal transition(EMT)during development and tumor aggressiveness", Curr Drug Targets, 11, pp.745~751 (2010)
- Bao B, "Notch-1induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells", Cancer Lett, 307, pp.26~36 (2011)
- Chen W, "Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells", J Transl Med, 13, pp.167~ (2015)
- Zhang Y, "Notch1 regulates the growth of human colon cancers", Cancer, 116, pp.5207~5218 (2010)
- Wang Z, "Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells", Cancer Res, 66, pp.2778~2784 (2006)
- Ferretti E, "Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors", J Clin Endocrinol Metab, 93, pp.4080~4087 (2008)
- Xiao X, "Notch1 mediates growth suppression of papillary and follicular thyroid cancer cells by histone deacetylase inhibitors", Mol Cancer Ther, 8, pp.350~356 (2009)
- Vasko V, "Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion", Proc Natl Acad Sci U S A, 104, pp.2803~2808 (2007)
- Su BH, "NOTCH1signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma", Oncotarget, 5, pp.6885~6895 (2014)
- Miele L, "NOTCH signaling as a novel cancer therapeutic target", Curr Cancer Drug Targets, 6, pp.313~323 (2006)
- Saad S, "Notch mediated epithelial to mesenchymal transformation is associated with increased expression of the Snail transcription factor", Int J Biochem Cell Biol, 42, pp.1115~1122 (2010)
- Leong KG, "Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin", J Exp Med, 204, pp.2935~2948 (2007)
- Buehler D, "Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas", Mod Pathol, 26, pp.54~61 (2013)
- Jung CW, "Expression of cancer stem cell markers and epithelial-mesenchymal transition-related factors in anaplastic thyroid carcinoma", Int J Clin Exp Pathol, 8, pp.560~568 (2015)