Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines

作者: Yeo-Jin Choi , Ga-Young Baek , Hae-Ran Park , Sung-Kee Jo , Uhee Jung

DOI: 10.1371/JOURNAL.PONE.0147343

关键词:

摘要: The control of radioresistance and metastatic potential surviving cancer cells is important for improving eradication by radiotheraphy. distal-less homeobox2 (DLX2) gene encodes a homeobox transcription factor involved in morphogenesis its deregulation was found human solid tumors hematologic malignancies. Here we investigated the role DLX2 association with radiation-induced epithelial to mesenchymal transition (EMT) stem cell-like properties regulation Smad2/3 signaling irradiated A549 MDA-MB-231 cell lines. In cells, EMT induced as demonstrated marker expression, phosphorylation Smad2/3, migratory invasive ability. Also, showed increased (CSCs) marker. Interestingly, overexpressed upon irradiation. Therefore, examined radioresistance. overexpression alone EMT, migration invasion, CSC expression. reduced colony-forming ability partially restored overexpression. On other hand, depletion using si-RNA abolished cells. radiation sensitivity both Moreover, knockdown key activator TGF-β1 pathway, abrogated indicating that expression dependent on signaling. These results plays crucial radioresistance, regulated

参考文章(45)
Laura Paleari, Giovanni Levi, Stefano Mantero, Giorgio R. Merlo, Sonya Trombino, Barbara Zerega, Multiple functions of Dlx genes. The International Journal of Developmental Biology. ,vol. 44, pp. 619- 626 ,(2000) , 10.1387/IJDB.11061425
Yoshifumi Itoh, Hideaki Nagase, Matrix metalloproteinases in cancer. Essays in Biochemistry. ,vol. 38, pp. 21- 36 ,(2002) , 10.1042/BSE0380021
Gerald J. Prud’homme, Cancer Stem Cells and Novel Targets for Antitumor Strategies Current Pharmaceutical Design. ,vol. 18, pp. 2838- 2849 ,(2012) , 10.2174/138161212800626120
Thomas Brabletz, Andreas Jung, Simone Spaderna, Falk Hlubek, Thomas Kirchner, Migrating cancer stem cells — an integrated concept of malignant tumour progression Nature Reviews Cancer. ,vol. 5, pp. 744- 749 ,(2005) , 10.1038/NRC1694
Yasuo Yoshioka, Kazuhiko Ogawa, Fumiaki Isohashi, Hideya Yamazaki, Yuji Seo, Ken Yoshida, Radiotherapy Targeting Cancer Stem Cells: Current Views and Future Perspectives Anticancer Research. ,vol. 33, pp. 747- 754 ,(2013)
Carl-Henrik Heldin, Maréne Landström, Aristidis Moustakas, Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Current Opinion in Cell Biology. ,vol. 21, pp. 166- 176 ,(2009) , 10.1016/J.CEB.2009.01.021
Christina Scheel, Robert A. Weinberg, Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Seminars in Cancer Biology. ,vol. 22, pp. 396- 403 ,(2012) , 10.1016/J.SEMCANCER.2012.04.001
Ze-yang Ding, Guan-nan Jin, Hui-fang Liang, Wei Wang, Wei-xun Chen, Pran K. Datta, Ming-zhi Zhang, Bixiang Zhang, Xiao-ping Chen, Transforming growth factor β induces expression of connective tissue growth factor in hepatic progenitor cells through Smad independent signaling. Cellular Signalling. ,vol. 25, pp. 1981- 1992 ,(2013) , 10.1016/J.CELLSIG.2013.05.027
Michael Baumann, Mechthild Krause, CD44 - a cancer stem cell related biomarker with predictive potential for radiotherapy Clinical Cancer Research. ,vol. 16, pp. 5091- 5093 ,(2010) , 10.1158/1078-0432.CCR-10-2244
Manav Korpal, Esther S. Lee, Guohong Hu, Yibin Kang, The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry. ,vol. 283, pp. 14910- 14914 ,(2008) , 10.1074/JBC.C800074200