Knock out CD44 in reprogrammed liver cancer cell C3A increases CSCs stemness and promotes differentiation

作者: Shuo Han , Jinhai Guo , Yinan Liu , Zhi Zhang , Qihua He

DOI: 10.18632/ONCOTARGET.6090

关键词: SOX2Homeobox protein NANOGKLF4Stem cellPathologyCellular differentiationStem cell markerCD44Cancer stem cellCancer researchMedicineOncology

摘要: CD44 is a widely known cancer stem cells marker in various cancers and validated to function tumor growth, survival metastasis. In this study, we first established C3A-derived liver by OSKM method [OCT4, SOX2, KLF4, c-MYC], termed C3A-induced (C3A-iCSCs) which acquired self-renewal stemness abilities. Then found was positive C3A-iCSCs mainly located cell nuclear. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) results showed nuclear combined promoter regions of c-MYC SOX2. These suggested that participated transcriptional regulation. To explore overall influence cells, knocked out using CRISPR/Cas9 technology. Our dramatic increase the expression markers OCT4, SOX2 NANOG CD44- compared with CD44+ C3A-iCSCs. Tumor derived from also displayed well-differentiated C3A-iCSCs, exhibited lower malignant degree. data indicated responsible for poorly differentiated highly maintenance low state.

参考文章(39)
Le Cong, Feng Zhang, Genome engineering using CRISPR-Cas9 system. Methods of Molecular Biology. ,vol. 1239, pp. 197- 217 ,(2015) , 10.1007/978-1-4939-1862-1_10
Atsushi Suetsugu, Masahito Nagaki, Hitomi Aoki, Tsutomu Motohashi, Takahiro Kunisada, Hisataka Moriwaki, Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells Biochemical and Biophysical Research Communications. ,vol. 351, pp. 820- 824 ,(2006) , 10.1016/J.BBRC.2006.10.128
Yaser Atlasi, Seyed J Mowla, Seyed AM Ziaee, Ahmad‐Reza Bahrami, None, OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer International Journal of Cancer. ,vol. 120, pp. 1598- 1602 ,(2007) , 10.1002/IJC.22508
Taro Yamashita, Xin Wei Wang, Cancer stem cells in the development of liver cancer Journal of Clinical Investigation. ,vol. 123, pp. 1911- 1918 ,(2013) , 10.1172/JCI66024
Jungsun Kim, John P. Hoffman, R. Katherine Alpaugh, Andrew D. Rhim, Maximilian Reichert, Ben Z. Stanger, Emma E. Furth, Antonia R. Sepulveda, Chao-Xing Yuan, Kyoung-Jae Won, Greg Donahue, Jessica Sands, Andrew A. Gumbs, Kenneth S. Zaret, An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression Cell Reports. ,vol. 3, pp. 2088- 2099 ,(2013) , 10.1016/J.CELREP.2013.05.036
Xin–Yuan Guan, Stephanie Ma, Kwok–Wah Chan, Liang Hu, Terence Kin–Wah Lee, Jana Yim–Hung Wo, Irene Oi–Lin Ng, Bo–Jian Zheng, Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. ,vol. 132, pp. 2542- 2556 ,(2007) , 10.1053/J.GASTRO.2007.04.025
Mina Komuta, Bart Spee, Sara Vander Borght, Rita De Vos, Chris Verslype, Raymond Aerts, Hirohisa Yano, Tetsuya Suzuki, Masanori Matsuda, Hideki Fujii, Valeer J. Desmet, Masamichi Kojiro, Tania Roskams, Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin Hepatology. ,vol. 47, pp. 1544- 1556 ,(2008) , 10.1002/HEP.22238
James O’Malley, Stavroula Skylaki, Kumiko A. Iwabuchi, Eleni Chantzoura, Tyson Ruetz, Anna Johnsson, Simon R. Tomlinson, Sten Linnarsson, Keisuke Kaji, High-resolution analysis with novel cell-surface markers identifies routes to iPS cells Nature. ,vol. 499, pp. 88- 91 ,(2013) , 10.1038/NATURE12243
M. Al-Hajj, M. S. Wicha, A. Benito-Hernandez, S. J. Morrison, M. F. Clarke, Prospective identification of tumorigenic breast cancer cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 3983- 3988 ,(2003) , 10.1073/PNAS.0530291100
Shigeo Takaishi, Tomoyuki Okumura, Shuiping Tu, Sophie S.W. Wang, Wataru Shibata, Ramanathan Vigneshwaran, Shanisha A.K. Gordon, Yutaka Shimada, Timothy C. Wang, Identification of Gastric Cancer Stem Cells Using the Cell Surface Marker CD44 Stem Cells. ,vol. 27, pp. 1006- 1020 ,(2009) , 10.1002/STEM.30