Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANGZhi-hai ¹ , LIZhong ¹ , YANGQing-jie ² , GUOMing ²

1. Department of Cardiothoracic Surgery, PLA 174 th Clinical College of Anhui Medical University, Xiamen 361000 Fujian, P. R. China;
2. Department of Cardiothoracic Surgery, The Success Hospital Affiliated Xiamen University, Xiamen 361000 Fujian, P. R. China;

Corresponding?author：

Keywords：

Ovol2 gene; Epithelial-mesenchymal transition (EMT); Lung adenocarcinoma; Distant metastasis; Migration

DOI：

10.7507/1007-4848.20160038

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. Methods A549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. Results After treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. Conclusion Overexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.

Citation： WANGZhi-hai, LIZhong, YANGQing-jie, GUOMing. Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(2): 173-177. doi: 10.7507/1007-4848.20160038 Copy

1.	Garfinkel MD, Wang J, Liang Y, et al. Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster: relationship to genetic complexity. Mol Cell Biol, 1994, 14(10): 6809-6818.
2.	Mevel-Ninio M, Terracol R, Kafatos FC. The ovo gene of Drosop-hilaencodes a zinc finger protein required for female germ line development. Embo J, 1991, 10(8): 2259-2266.
3.	Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
4.	Unezaki S, Horai R, Sudo K, et al. Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mice. Genes Cells, 2007, 12(6): 773-785.
5.	Zhang T, Zhu Q, Xie Z, et al. The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. J Bio Chem, 2013, 288(9): 6166-6177.
6.	Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 2003, 112(12): 1776-1784.
7.	Nieto MA. The ins and outs of the epithelial to mesenchymal transi-tion in health and disease. Ann Rev Cell Dev Biol, 2011, 27: 347-376.
8.	Acloque H, Oca? a OH, Matheu A, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell, 2011, 21(3): 546-558.
9.	Roca H, Hernandez J, Weidner S, et al. Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer. PloS one, 2013, 8(10): e76773.
10.	Thiery JP, Acloque H, Huang RYJ, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
11.	Watanabe K, Villarreal-Ponce A, Sun P, et al. Mammary morpho-genesis and regeneration require the inhibition of EMT at terminal end buds by ovol2 transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
12.	Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
13.	Christofori G, Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 1999, 24(2): 73-76.
14.	孫威.非小細胞肺癌治療進展.中華現代外科學雜志, 2005, 2(1): 75-78.
15.	王玨, 郭占領.Ⅰ期至ⅢA期肺癌外科規范化治療的研究進展.中國胸心血管外科臨床雜志, 2014, 21(5): 675-680.
16.	Verdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe: a 2000-2002 period analysis of EUROCARE-4 data. Lancet Oncol, 2007, 8(9): 784-796.
17.	Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell, 2006, 127(4): 679-695.
18.	Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006, 7(2): 131-142.
19.	Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, et al. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle, 2010, 9(22): 4461-4468.
20.	Li L, Li W. Epithelial-mesenchymal transition in human cancer: Comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther, 2015, 150: 33-46.
21.	Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene, 2005, 24(50): 7443-7454.
22.	Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
23.	Payre F, Vincent A, Carreno S. Ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature, 1999, 400(6741): 271-275.
24.	Christina S, Elinor Ng E, Sophia Hsin-Jung L, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
25.	Watanabe K, Villarreal-Ponce A, Sun P. Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
26.	吳躍超. Ovol2在人乳腺癌細胞中抑制TGF-b信號通路的分子機制研究.廈門大學:廈門大學學位論文. 2014.
27.	田茗源, 王林輝, 張雄, 等.肺癌組織中E-cadherin和Vimentin的表達及其與上皮-間質轉化的相關性.中國生物制品學雜志, 2011, 24(9): 1068-1071.
28.	郭凱, 王曉東.肺癌組織中EMT相關蛋白的表達變化及意義[J].山東醫藥, 2012, 52(2): 70-71.
29.	黃振杰, 鄭金旭, 湯艷, 等.肺泡上皮細胞間質轉化對肺癌細胞轉移影響的研究.中華腫瘤防治雜志, 2011, 18(16): 1230-1234.
30.	李洪利, 尹崇高, 李文通, 等.過表達Snail增強肺癌細胞A549的體外侵襲能力.中國生物化學與分子生物學報, 2010, 10: 943-948.
31.	孫菊杰, 魏玲, 張德賢, 等.非小細胞肺癌Twist表達與EMT相關性分析.中華腫瘤防治雜志, 2014, 21(16): 13.

1. Garfinkel MD, Wang J, Liang Y, et al. Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster: relationship to genetic complexity. Mol Cell Biol, 1994, 14(10): 6809-6818.
2. Mevel-Ninio M, Terracol R, Kafatos FC. The ovo gene of Drosop-hilaencodes a zinc finger protein required for female germ line development. Embo J, 1991, 10(8): 2259-2266.
3. Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
4. Unezaki S, Horai R, Sudo K, et al. Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mice. Genes Cells, 2007, 12(6): 773-785.
5. Zhang T, Zhu Q, Xie Z, et al. The zinc finger transcription factor Ovol2 acts downstream of the bone morphogenetic protein pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. J Bio Chem, 2013, 288(9): 6166-6177.
6. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 2003, 112(12): 1776-1784.
7. Nieto MA. The ins and outs of the epithelial to mesenchymal transi-tion in health and disease. Ann Rev Cell Dev Biol, 2011, 27: 347-376.
8. Acloque H, Oca? a OH, Matheu A, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell, 2011, 21(3): 546-558.
9. Roca H, Hernandez J, Weidner S, et al. Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer. PloS one, 2013, 8(10): e76773.
10. Thiery JP, Acloque H, Huang RYJ, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5): 871-890.
11. Watanabe K, Villarreal-Ponce A, Sun P, et al. Mammary morpho-genesis and regeneration require the inhibition of EMT at terminal end buds by ovol2 transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
12. Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett, 2002, 176(2): 123-128.
13. Christofori G, Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci 1999, 24(2): 73-76.
14. 孫威.非小細胞肺癌治療進展.中華現代外科學雜志, 2005, 2(1): 75-78.
15. 王玨, 郭占領.Ⅰ期至ⅢA期肺癌外科規范化治療的研究進展.中國胸心血管外科臨床雜志, 2014, 21(5): 675-680.
16. Verdecchia A, Francisci S, Brenner H, et al. Recent cancer survival in Europe: a 2000-2002 period analysis of EUROCARE-4 data. Lancet Oncol, 2007, 8(9): 784-796.
17. Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell, 2006, 127(4): 679-695.
18. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006, 7(2): 131-142.
19. Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, et al. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle, 2010, 9(22): 4461-4468.
20. Li L, Li W. Epithelial-mesenchymal transition in human cancer: Comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther, 2015, 150: 33-46.
21. Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene, 2005, 24(50): 7443-7454.
22. Mackay DR, Hu M, Li B, et al. The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol, 2006, 291(1): 38-52.
23. Payre F, Vincent A, Carreno S. Ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature, 1999, 400(6741): 271-275.
24. Christina S, Elinor Ng E, Sophia Hsin-Jung L, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
25. Watanabe K, Villarreal-Ponce A, Sun P. Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2transcriptional repressor. Dev Cell, 2014, 29(1): 59-74.
26. 吳躍超. Ovol2在人乳腺癌細胞中抑制TGF-b信號通路的分子機制研究.廈門大學:廈門大學學位論文. 2014.
27. 田茗源, 王林輝, 張雄, 等.肺癌組織中E-cadherin和Vimentin的表達及其與上皮-間質轉化的相關性.中國生物制品學雜志, 2011, 24(9): 1068-1071.
28. 郭凱, 王曉東.肺癌組織中EMT相關蛋白的表達變化及意義[J].山東醫藥, 2012, 52(2): 70-71.
29. 黃振杰, 鄭金旭, 湯艷, 等.肺泡上皮細胞間質轉化對肺癌細胞轉移影響的研究.中華腫瘤防治雜志, 2011, 18(16): 1230-1234.
30. 李洪利, 尹崇高, 李文通, 等.過表達Snail增強肺癌細胞A549的體外侵襲能力.中國生物化學與分子生物學報, 2010, 10: 943-948.
31. 孫菊杰, 魏玲, 張德賢, 等.非小細胞肺癌Twist表達與EMT相關性分析.中華腫瘤防治雜志, 2014, 21(16): 13.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Overexpress Ovol2 Gene Inhibiting the Migration and Invasion Ability of Lung Adeno-carcinoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content