Up-Regulation Expressions of Snail and N-cadherin in Thyroid Papillary Carcinoma and Their Clinical Significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGXiang-shan ¹ ,  CHENGShao-mei ² , XIAORui-xue ¹ , ZHANGJing ¹ , XIAZhen ¹ , WANGXue ¹

1. Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031, Shandong Province, China;
2. Department of Gynecology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031, Shandong Province, China;

Corresponding?author：

CHENGShao-mei, Email: 1124431252@qq.com

Keywords：

Snail; N-cadherin; Papillary thyroid carcinoma; Metastasis

DOI：

10.7507/1007-9424.20150050

Video：

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Objective To investigate the expressions of Snail and N-cadherin protein in thyroid papillary carcinoma (PTC) tissues and cell lines, and then discuss the clinical value of Snail and N-cadherin expressions. Methods Immunohis-tochemical SP technique was performed to detect the expressions of Snail and N-cadherin protein in 60 cases of PTC, and the relation between the expression of Snail or N-cadherin and clinicopathologic indicators was analyzed. Western blot was used to investigate the constitutive and inducible expressions of Snail and N-cadherin protein. Results ①The positive rates of Snail and N-cadherin protein expressions were 85.0% (51/60) and 78.3% (47/60) respectively in the PTC tissues of 60 patients with PTC, which were significantly higher than those (0, 0, respectively) in the corresponding normal tissues adjacent to the cancer (P < 0.01).②The positive rates of Snail and N-cadherin protein expressions in the PTC with lymph node metastasis were significantly higher than those in the PTC without lymph node metastasis (P < 0.01), which were not related with the gender, age, tumor size of the patients (P > 0.01).③There was a positive correlation between Snail and N-cadherin protein positive expression (r_s=0.721, P < 0.001).④The constitutive and inducible expressions of Snail and N-cadherin in the PTC tissues and cell lines further were identified by Western blot. Conclusions Snail and N-cadherin could constitutively express in PTC, which might play important roles in the development and metastasis of PTC. Snail and N-cadherin might be used as effective indicators.

Citation： YANGXiang-shan, CHENGShao-mei, XIAORui-xue, ZHANGJing, XIAZhen, WANGXue. Up-Regulation Expressions of Snail and N-cadherin in Thyroid Papillary Carcinoma and Their Clinical Significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(2): 181-185. doi: 10.7507/1007-9424.20150050 Copy

1.	?楊香山, 范開席, 李成軍, 等.膜表面核仁素參與表皮生長因子受體信號啟動的研究.中國普外基礎與臨床雜志, 2013, 20(10): 1117-1121.
2.	楊香山, 程紹梅, 郭京艷, 等.接合物蛋白在甲狀腺乳頭狀微小癌中的表達及其臨床意義.中國全科醫學雜志, 2013, 16(10): 3444-3446.
3.	Bracke ME, Depypere H, Labit C, et al. Functional downregulation of the E-cadherin/catenin complex leads to loss of contact inhibition of motility and of mitochondrial activity, but not of growth in confluent epithelial cell cultures. Eur J Cell Biol, 1997, 74(4): 342-349.
4.	Ma J, Zhang L, Ru GQ, et al. Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts poor prognosis in gastric carcinoma. World J Gastroenterol, 2007, 13(11): 1680-1686.
5.	Ma?tre JL, Heisenberg CP. Three functions of cadherins in cell adhesion. Curr Biol, 2013, 23(14): R626-R633.
6.	Nishioka R, Itoh S, Gui T, et al. SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. Exp Mol Pathol, 2010, 89(2): 149-157.
7.	van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer, 2014, 14(2): 121-134.
8.	Suyama K, Shapiro I, Guttman M, et al. A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell, 2002, 2(4): 301-314.
9.	Batlle E, Sancho E, Francí C, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol, 2000, 2(2): 84-89.
10.	Li G, Satyamoorthy K, Herlyn M. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res, 2001, 61(9): 3819-3825.
11.	Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
12.	Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol, 2008, 10(3): 295-305.
13.	Harris AL. Hypoxia－A key regulatory factor in tumour growth. Nat Rev Cancer, 2002, 2(1): 38-47.
14.	Semenza GL. Hypoxia-inducible factor 1: Oxygen homeostasis and disease pathophysiology. Trends Mol Med, 2001, 7(8): 345-350.
15.	Ji RC. Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. Cancer Lett, 2014, 346(1): 6-16.
16.	Masui T, Ota I, Yook JI, et al. Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells. Int J Oncol, 2014, 44(3): 693-699.
17.	包俊杰, 吳誠義. E-cadherin及N-cadherin在乳腺癌中表達的相關性及臨床意義.中國普通外科雜志, 2010, 19(11): 1253-1256.
18.	Cheng CW, Wu PE, Yu JC, et al. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 2001, 20(29): 3814-3823.
19.	Van Aken E, De Wever O, Correia da Rocha AS, et al. Defective E-cadherin/catenin complexes in human cancer. Virchows Arch, 2001, 439(6): 725-751.
20.	Sánchez-Tilló E, Liu Y, de Barrios O, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci, 2012, 69(20): 3429-3456.
21.	Gheldof A, Berx G. Cadherins and epithelial-to-mesenchymal transition. Prog Mol Biol Transl Sci, 2013, 116: 317-336.

1. ?楊香山, 范開席, 李成軍, 等.膜表面核仁素參與表皮生長因子受體信號啟動的研究.中國普外基礎與臨床雜志, 2013, 20(10): 1117-1121.
2. 楊香山, 程紹梅, 郭京艷, 等.接合物蛋白在甲狀腺乳頭狀微小癌中的表達及其臨床意義.中國全科醫學雜志, 2013, 16(10): 3444-3446.
3. Bracke ME, Depypere H, Labit C, et al. Functional downregulation of the E-cadherin/catenin complex leads to loss of contact inhibition of motility and of mitochondrial activity, but not of growth in confluent epithelial cell cultures. Eur J Cell Biol, 1997, 74(4): 342-349.
4. Ma J, Zhang L, Ru GQ, et al. Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts poor prognosis in gastric carcinoma. World J Gastroenterol, 2007, 13(11): 1680-1686.
5. Ma?tre JL, Heisenberg CP. Three functions of cadherins in cell adhesion. Curr Biol, 2013, 23(14): R626-R633.
6. Nishioka R, Itoh S, Gui T, et al. SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. Exp Mol Pathol, 2010, 89(2): 149-157.
7. van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer, 2014, 14(2): 121-134.
8. Suyama K, Shapiro I, Guttman M, et al. A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell, 2002, 2(4): 301-314.
9. Batlle E, Sancho E, Francí C, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol, 2000, 2(2): 84-89.
10. Li G, Satyamoorthy K, Herlyn M. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res, 2001, 61(9): 3819-3825.
11. Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
12. Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol, 2008, 10(3): 295-305.
13. Harris AL. Hypoxia－A key regulatory factor in tumour growth. Nat Rev Cancer, 2002, 2(1): 38-47.
14. Semenza GL. Hypoxia-inducible factor 1: Oxygen homeostasis and disease pathophysiology. Trends Mol Med, 2001, 7(8): 345-350.
15. Ji RC. Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis. Cancer Lett, 2014, 346(1): 6-16.
16. Masui T, Ota I, Yook JI, et al. Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells. Int J Oncol, 2014, 44(3): 693-699.
17. 包俊杰, 吳誠義. E-cadherin及N-cadherin在乳腺癌中表達的相關性及臨床意義.中國普通外科雜志, 2010, 19(11): 1253-1256.
18. Cheng CW, Wu PE, Yu JC, et al. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 2001, 20(29): 3814-3823.
19. Van Aken E, De Wever O, Correia da Rocha AS, et al. Defective E-cadherin/catenin complexes in human cancer. Virchows Arch, 2001, 439(6): 725-751.
20. Sánchez-Tilló E, Liu Y, de Barrios O, et al. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci, 2012, 69(20): 3429-3456.
21. Gheldof A, Berx G. Cadherins and epithelial-to-mesenchymal transition. Prog Mol Biol Transl Sci, 2013, 116: 317-336.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Up-Regulation Expressions of Snail and N-cadherin in Thyroid Papillary Carcinoma and Their Clinical Significances

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