Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma
Open accessAbstract
Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem-cell–related genes are preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not known whether or how these cancer cells contribute to tumor initiation and progression. Here, our data showed that increased expression of pluripotency transcription factor Nanog in cancer cells correlates with a worse clinical outcome in HCC. Using the Nanog promoter as a reporter system, we could successfully isolate a small subpopulation of Nanog-positive cells. We demonstrate that Nanog-positive cells exhibited enhanced ability of self-renewal, clonogenicity, and initiation of tumors, which are consistent with crucial hallmarks in the definition of cancer stem cells (CSCs). NanogPos CSCs could differentiate into mature cancer cells in in vitro and in vivo conditions. In addition, we found that NanogPos CSCs exhibited resistance to therapeutic agents (e.g., sorafenib and cisplatin) and have a high capacity for tumor invasion and metastasis. Knock-down expression of Nanog in NanogPos CSCs could decrease self-renewal accompanied with decreased expression of stem-cell–related genes and increased expression of mature hepatocyte-related genes. Overexpression of Nanog in NanogNeg cells could restore self-renewal. Furthermore, we found that insulin-like growth factor (IGF)2 and IGF receptor (IGF1R) were up-regulated in NanogPos CSCs. Knock-down expression of Nanog in NanogPos CSCs inhibited the expression of IGF1R, and overexpression of Nanog in NanogNeg cells increased the expression of IGF1R. A specific inhibitor of IGF1R signaling could significantly inhibit self-renewal and Nanog expression, indicating that IGF1R signaling participated in Nanog-mediated self-renewal. Conclusion : These data indicate that Nanog could be a novel biomarker for CSCs in HCC, and that Nanog could play a crucial role in maintaining the self-renewal of CSCs through the IGF1R-signaling pathway.
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Human V. vulnificus infections and their laboratory models often terminate in septic shock.
“Human infections with V. vulnificus and their laboratory models often terminate in septic shock (Shan et al., 2012).”
From Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus (2015) · cites this paper as Shan et al., 2012
The Materials and Methods section describes human hepatocellular carcinoma specimens and cell cultures, while the Discussion passages concern Nanog and cancer-cell experiments. Searches for “V. vulnificus septic shock” and “human infections laboratory models terminate in septic shock” found no passage about Vibrio vulnificus infections or septic shock in our copy. (LLM, conf=0.77)
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The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M. W., Reinhard, F., Zhang, C. C., Shipitsin, M. V., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.027 · Cited by 8,679 · see citing works
Cancer stem cells in solid tumours: accumulating evidence and unresolved questions
Visvader, J., & Lindeman, G. (2008) · Nature Reviews. Cancer · doi:10.1038/nrc2499 · Cited by 3,562 · see citing works
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
Polyak, K., & Weinberg, R. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2620 · Cited by 3,302 · see citing works
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
Singh, A., & Settleman, J. (2010) · Oncogene · doi:10.1038/onc.2010.215 · Cited by 2,545 · see citing works
Hepatocellular carcinoma pathogenesis: from genes to environment
Farazi, P. A., & DePinho, R. A. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1934 · Cited by 1,979 · see citing works
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
Vermeulen, L., De Sousa E Melo, F., van der Heijden, M., Cameron, K., de Jong, J. H., Borovski, T., Tuynman, J. B., Todaro, M., Merz, C., Rodermond, H., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2048 · Cited by 1,804 · see citing works
Significance of CD90+ Cancer Stem Cells in Human Liver Cancer
Yang, Z. F., Ho, D. W., Ng, M. N., Lau, C. K., Yu, W. C., Ngai, P., Chu, P., Lam, C. T., Poon, R. T. P., & Fan, S. T. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.01.013 · Cited by 1,188 · see citing works
Self-citationHeterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution
Shackleton, M. J., Quintana, E., Fearon, E. R., & Morrison, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.08.017 · Cited by 1,152 · see citing works
Yamashita, T., Ji, J., Budhu, A., Forgues, M., Yang, W., Wang, H., Jia, H., Ye, Q., Qin, L., Wauthier, E., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.12.004 · Cited by 1,142 · see citing works
Lin28 promotes transformation and is associated with advanced human malignancies
Viswanathan, S. R., Powers, J. T., Einhorn, W. S., Hoshida, Y., Ng, T., Toffanin, S., O’Sullivan, M. J., Lü, J., Phillips, L. A., Lockhart, V. L., et al. (2009) · Nature Genetics · doi:10.1038/ng.392 · Cited by 816 · see citing works
Module map of stem cell genes guides creation of epithelial cancer stem cells.
Wong, D. J., Liu, H., Ridky, T. W., Cassarino, D., Segal, E., & Chang, H. Y. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.02.009 · Cited by 741 · see citing works
The Increasing Complexity of the Cancer Stem Cell Paradigm
Rosen, J. M., & Jordan, C. T. (2009) · Science · doi:10.1126/science.1171837 · Cited by 699 · see citing works
Kim, J., Woo, A., Chu, J., Snow, J. W., Fujiwara, Y., Kim, C., Cantor, A., & Orkin, S. (2010) · Cell · doi:10.1016/j.cell.2010.09.010 · Cited by 670 · see citing works
Chiou, S., Yu, C.-C., Huang, C.-Y., Lin, S., Liu, C., Tsai, T., Chou, S.-H., Chien, C., Ku, H., & Lo, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4404 · Cited by 640 · see citing works
CD13 is a therapeutic target in human liver cancer stem cells
Haraguchi, N., Ishii, H., Mimori, K., Tanaka, F., Ohkuma, M., Kim, H. M., Akita, H., Takiuchi, D., Hatano, H., Nagano, H., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42550 · Cited by 604 · see citing works
Bendall, S. C., Stewart, M. H., Menéndez, P. R., George, D., Vijayaragavan, K., Werbowetski‐Ogilvie, T. E., Ramos–Mejía, V., Rouleau, A., Yang, J., Bosse, M. M., et al. (2007) · Nature · doi:10.1038/nature06027 · Cited by 588 · see citing works
Lee, T. K., Castilho, A., Cheung, V. C. H., Tang, K. H., Ma, S., & Ng, I. O. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.06.005 · Cited by 586 · see citing works
Dallas, N. A., Xia, L., Fan, F., Gray, M. J., Gaur, P., Buren, G. V., Samuel, S., Kim, M. P., Lim, S. J., & Ellis, L. M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2023 · Cited by 573 · see citing works
Dysregulation of growth factor signaling in human hepatocellular carcinoma
Breuhahn, K., Longerich, T., & Schirmacher, P. (2006) · Oncogene · doi:10.1038/sj.onc.1209556 · Cited by 392 · see citing works
Ma, S., Tang, K. H., Chan, Y. P., Lee, T. K., Kwan, P. S., Castilho, A., Ng, I. O., Man, K., Wong, N., To, K., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.11.010 · Cited by 383 · see citing works
Somervaille, T., Matheny, C., Spencer, G. J., Iwasaki, M., Rinn, J., Witten, D., Chang, H. Y., Shurtleff, S., Downing, J., & Cleary, M. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2008.11.015 · Cited by 379 · see citing works
Functional Evidence that the Self-Renewal Gene NANOG Regulates Human Tumor Development
Jeter, C. R., Badeaux, M. D., Choy, G. S., Chandra, D., Patrawala, L., Liu, C., Calhoun‐Davis, T., Zaehres, H., Daley, G. Q., & Tang, D. G. (2009) · Stem Cells · doi:10.1002/stem.29 · Cited by 335 · see citing works
Liver stem cells and hepatocellular carcinoma†
Mishra, L., Banker, T. P., Murray, J. C., Byers, S. W., Thenappan, A., He, A. R., Shetty, K., Johnson, L. B., & Reddy, E. P. (2008) · Hepatology · doi:10.1002/hep.22704 · Cited by 333 · see citing works
Progenitor/stem cells give rise to liver cancer due to aberrant TGF-β and IL-6 signaling
Tang, Y., Kitisin, K., Jogunoori, W. S., Li, C., Deng, C., Mueller, S. C., Ressom, H. W., Rashid, A., He, A. R., Mendelson, J. S., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705395105 · Cited by 312 · see citing works
Zbinden, M., Duquet, A., Lorente‐Trigos, A., Bikeye, S.-N. N., Borges, I., & Altaba, A. R. I. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.137 · Cited by 307 · see citing works
Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency
Hotta, A., Cheung, A. Y. L., Farra, N., Vijayaragavan, K., Séguin, C. A., Draper, J. S., Pasceri, P., Maksakova, I. A., Mager, D. L., Rossant, J., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1325 · Cited by 298 · see citing works
Embryonic stem cell markers expression in cancers
Schoenhals, M. J., Kassambara, A., Vos, J. D., Hose, D., Moreaux, J., & Klein, B. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.02.156 · Cited by 261 · see citing works
Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer
Meng, H.-M., Zheng, P., Wang, X., Liu, C., Sui, H., Wu, S., Zhou, J., Ding, Y., & Li, J. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.9.4.10666 · Cited by 220 · see citing works
Marquardt, J. U., Galle, P. R., & Teufel, A. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.07.007 · Cited by 195 · see citing works
Expression of Pluripotent Stem Cell Reprogramming Factors by Prostate Tumor Initiating Cells
Bae, K., Su, Z. Z., Frye, C., McClellan, S., Allan, R. W., Andrejewski, J. T., Kelley, V., Jorgensen, M., Steindler, D. A., Vieweg, J., et al. (2010) · The Journal of Urology · doi:10.1016/j.juro.2009.12.092 · Cited by 126 · see citing works
Yan, X. S., Ma, L., Yi, D., Yoon, J.-G., Diercks, A. H., Foltz, G., Price, N. D., Hood, L., & Tian, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018696108 · Cited by 125 · see citing works
Self-citationNussbaum, T., Samarin, J., Ehemann, V., Bissinger, M., Ryschich, E., Khamidjanov, A., Yu, X., Gretz, N., Schirmacher, P., & Breuhahn, K. (2008) · Hepatology · doi:10.1002/hep.22297 · Cited by 101 · see citing works
Liu, Y., Clem, B. F., Zuba‐Surma, E. K., El‐Naggar, S., Telang, S., Jenson, A. B., Wang, Y., Shao, H., Ratajczak, M. Z., Chesney, J. A., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.02.015 · Cited by 92 · see citing works
Hedgehog/GLI1 regulates IGF dependent malignant behaviors in glioma stem cells
Hsieh, A., Ellsworth, R., & Hsieh, D. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22433 · Cited by 89 · see citing works
Nanog transforms NIH3T3 cells and targets cell-type restricted genes
Piestun, D., Kochupurakkal, B. S., Jacob‐Hirsch, J., Zeligson, S., Koudritsky, M., Domany, E., Amariglio, N., Rechavi, G., & Givol, D. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.152 · Cited by 72 · see citing works
The identification of stem cells in human liver diseases and hepatocellular carcinoma
Oliva, J., French, B. A., Qing, X., & French, S. W. (2010) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2010.01.003 · Cited by 44 · see citing works
Li, Y., & Geng, Y. (2010) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2010.09.005 · Cited by 35 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Kim J, Woo AJ, Chu J, Snow JW, Fujiwara Y, Kim CG, et al. A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 2010;143:313-324.
Cited by
Sorted by citations
Epigenetic modulators, modifiers and mediators in cancer aetiology and progression
Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.13 · Cited by 878 · see citing works
Sustained proliferation in cancer: Mechanisms and novel therapeutic targets
Feitelson, M. A., Arzumanyan, A. L., Kulathinal, R. J., Blain, S. W., Holcombe, R. F., Mahajna, J. A., Marino, M., Martínez‐Chantar, M. L., Nawroth, R., Sánchez-Garcı́a, I., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.02.006 · Cited by 783 · see citing works
Cancer stem cells in hepatocellular carcinoma — from origin to clinical implications
Lee, T. K., Guan, X., & Ma, S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00508-3 · Cited by 463 · see citing works
Chen, W.-J., Ho, C., Chang, Y., Chen, H., Ling, T., Ling, T., Yuan, S., Yuan, S.-S., Chen, Y.-J. L., Lin, C.-Y., et al. (2014) · Nature Communications · doi:10.1038/ncomms4472 · Cited by 442 · see citing works
Insulin Receptor Isoforms in Physiology and Disease: An Updated View
Belfiore, A., Malaguarnera, R., Vella, V., Lawrence, M. C., Sciacca, L., Frasca, F., Morrione, A., & Vigneri, R. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00073 · Cited by 376 · see citing works
Mechanisms of drug resistance in HCC
Ladd, A. D., Duarte, S. M., Şahin, İ., & Zarrinpar, A. (2023) · Hepatology · doi:10.1097/hep.0000000000000237 · Cited by 379 · see citing works
Yuan, J.-H., Liu, X.-N., Wang, T.-T., Pan, W., Tao, Q.-F., Zhou, W.-P., Wang, F., & Sun, S.-H. (2017) · Nature Cell Biology · doi:10.1038/ncb3538 · Cited by 367 · see citing works
Denduluri, S. K., Idowu, O. A., Wang, Z., Liao, Z., Yan, Z., Mohammed, M. K., Ye, J., Wei, Q., Wang, J., Zhao, L., et al. (2014) · Genes & Diseases · doi:10.1016/j.gendis.2014.10.004 · Cited by 333 · see citing works
The evolving concept of liver cancer stem cells
Nio, K., Yamashita, T., & Kaneko, S. (2017) · Molecular Cancer · doi:10.1186/s12943-016-0572-9 · Cited by 271 · see citing works
Targeted therapy for hepatocellular carcinoma: Challenges and opportunities
Chen, S., Cao, Q., Wen, W., & Wang, H. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.114428 · Cited by 253 · see citing works
Chen, J., Jin, R., Zhao, J., Liu, J., Ying, H., Yan, H., Zhou, S., Liang, Y., Huang, D., Liang, X. H., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.06.019 · Cited by 253 · see citing works
Self-citationThe significance of intertumor and intratumor heterogeneity in liver cancer
Liu, J., Dang, H. T., & Wang, X. W. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.165 · Cited by 245 · see citing works
Self-citationJeter, C. R., Yang, T., Wang, J., Chao, H., & Tang, D. G. (2015) · Stem Cells · doi:10.1002/stem.2007 · Cited by 240 · see citing works
Wu, C. X., Wang, X. Q., Chok, K., Man, K., Tsang, S. H. Y., Chan, A. C. Y., Wing, K., Xia, W. G., & Cheung, T. T. (2018) · Theranostics · doi:10.7150/thno.25487 · Cited by 228 · see citing works
Arezes, J., Jung, G., Gabayan, V., Valore, E., Ruchala, P., Gulig, P. A., Ganz, T., Nemeth, E., & Bulut, Y. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2014.12.001 · Cited by 227 · see citing works
“Human infections with V. vulnificus and their laboratory models often terminate in septic shock (Shan et al., 2012).”
BackgroundPluripotency transcription factors and cancer stem cells: small genes make a big difference
Liu, A., Yu, X., & Liu, S. (2013) · 癌症：英文版 · doi:10.5732/cjc.012.10282 · Cited by 221 · see citing works
Tovar, V., Cornellà, H., Moeini, A., Vidal, S. J., Hoshida, Y., Sia, D., Peix, J., Cabellos, L., Alsinet, C., Torrecilla, S., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309501 · Cited by 206 · see citing works
Lo, J. H. T., Lau, E. Y.-T., Ching, R. H. H., Cheng, B. Y.-L., Ma, M. K. F., Ng, I. O., & Lee, T. K. (2015) · Hepatology · doi:10.1002/hep.27859 · Cited by 199 · see citing works
Niu, L., Liu, L., Yang, S., Ren, J., Lai, P. B. S., & Chen, G. G. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.10.002 · Cited by 198 · see citing works
Self-citationvan Schaijik, B., Davis, P. F., Wickremesekera, A., Tan, S. T., & Itinteang, T. (2017) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2017-204815 · Cited by 197 · see citing works
Liu, S., Li, N., Yu, X., Xiao, X., Cheng, K., Hu, J., Wang, J., Zhang, D., Cheng, S., & Liu, S. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.046 · Cited by 193 · see citing works
Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation
Farabaugh, S. M., Boone, D. N., & Lee, A. V. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00059 · Cited by 182 · see citing works
Yong, X., Tang, B., Xiao, Y., Xie, R., Qin, Y., Luo, G., Hu, C.-J., Dong, H. F., & Yang, S. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.02.032 · Cited by 175 · see citing works
Targeting cancer stem cells: emerging role of Nanog transcription factor
Wu, C., Wang, M., & Chiou, S.-H. (2013) · OncoTargets and Therapy · doi:10.2147/ott.s38114 · Cited by 171 · see citing works
Xu, Y., Huang, J., Ma, L., Shan, J., Shen, J., Yang, Z., Liu, L., Luo, Y., Yao, C., & Qian, C. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.11.034 · Cited by 165 · see citing works
Self-citationDiet and liver cancer risk: a narrative review of epidemiological evidence
Yang, W., Zeng, X., Liu, Z., Zhao, Q.-H., Tan, Y., Gao, J., Li, H., & Xiang, Y. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520001208 · Cited by 164 · see citing works
Liu, C., Liu, L., Chen, X., Shen, J., Shan, J., Xu, Y., Yang, Z., Wu, L., Xia, F., Bie, P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062828 · Cited by 161 · see citing works
Self-citationThe Links Between Insulin Resistance, Diabetes, and Cancer
Orgel, E., & Mittelman, S. D. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0356-6 · Cited by 163 · see citing works
Cancer stem cells (CSCs), cervical CSCs and targeted therapies
Huang, R., & Rofstad, E. K. (2016) · Oncotarget · doi:10.18632/oncotarget.10169 · Cited by 162 · see citing works
Simon, T. G., King, L. Y., Chong, D. Q., Nguyen, L. H., Ma, Y., VoPham, T., Giovannucci, E. L., Fuchs, C. S., Meyerhardt, J. A., Corey, K. E., et al. (2018) · Hepatology · doi:10.1002/hep.29660 · Cited by 160 · see citing works
Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells
Wang, R., Sun, Q., Wang, P., Liu, M., Xiong, S., Luo, J., Huang, H., Du, Q., Geller, D. A., & Cheng, B. (2015) · Oncotarget · doi:10.18632/oncotarget.6805 · Cited by 159 · see citing works
Liu, C., Liu, L., Chen, X., Cheng, J., Zhang, H., Shen, J., Shan, J., Xu, Y., Yang, Z., Lai, M., et al. (2016) · Hepatology · doi:10.1002/hep.28509 · Cited by 148 · see citing works
Self-citationThe Emerging Role of Insulin and Insulin-Like Growth Factor Signaling in Cancer Stem Cells
Malaguarnera, R., & Belfiore, A. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00010 · Cited by 144 · see citing works
WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells
Zhang, K., Guo, Y., Wang, X., Zhao, H., Ji, Z., Cheng, C., Li, L., Fang, Y., Xu, D., Zhu, H. H., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-1887 · Cited by 134 · see citing works
Emerging role of nanog in tumorigenesis and cancer stem cells
Santaliz-Ruiz, L. E. I., Xie, X., Old, M. O., Teknos, T. N., & Pan, Q. (2013) · International Journal of Cancer · doi:10.1002/ijc.28690 · Cited by 136 · see citing works
piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling
Peng, L., Song, L., Liu, C., Lv, X., Li, X., Jie, J., Zhao, D., & Li, D. (2015) · Tumor Biology · doi:10.1007/s13277-015-4056-0 · Cited by 129 · see citing works
The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells
Gawlik-Rzemieniewska, N., & Bednarek, I. A. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1121348 · Cited by 129 · see citing works
Liu, C., Liu, L., Chen, X., Cheng, J., Zhang, H., Zhang, C., Shan, J., Shen, J., & Qian, C. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1236 · Cited by 129 · see citing works
Self-citationLai, S.-C., Su, Y.-T., Chi, C.-C., Kuo, Y.-C., Lee, K.-F., Wu, Y.-C., Lan, P.-C., Yang, M.-H., Chang, T.-S., & Huang, Y.-H. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1442-2 · Cited by 128 · see citing works
Hepatocellular carcinoma and lifestyles
Saran, U., Humar, B., Kolly, P., & Dufour, J. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.028 · Cited by 125 · see citing works
Li, X., Chen, C. Y., Xiang, D., Qu, L., Sun, W. C., Lu, X., Zhou, T., Chen, S., Ning, B., Cheng, Z., et al. (2017) · Hepatology · doi:10.1002/hep.29372 · Cited by 125 · see citing works
Yao, C., Su, L., Shan, J., Zhu, C., Liu, L., Liu, C., Xu, Y., Yang, Z., Bian, X., Shao, J., et al. (2016) · Stem Cells · doi:10.1002/stem.2320 · Cited by 123 · see citing works
Self-citationLi, H., Batth, I. S., Qu, X., Xu, L., Song, N., Wang, R., & Liu, Y. (2017) · Molecular Cancer · doi:10.1186/s12943-016-0576-5 · Cited by 122 · see citing works
Xiong, S., Wang, R., Chen, Q., Luo, J., Wang, J., Zhao, Z., Li, Y., Wang, Y., Wang, X., & Cheng, B. (2018) · PubMed Central · Cited by 122 · see citing works
Lei, Z.-J., Wang, J., Xiao, H.-L., Guo, Y., Wang, T., Li, Q., Liu, L., Luo, X., Fan, L.-L., Li, L., et al. (2015) · Oncogene · doi:10.1038/onc.2015.129 · Cited by 116 · see citing works
Self-citationHuan, H.-B., Wen, X.-D., Chen, X., Wu, L., Wu, L., Zhang, L., Yang, D.-P., Zhang, X., Bie, P., Qian, C., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.08.016 · Cited by 117 · see citing works
Self-citationCancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies
Wang, N., Wang, S., Li, M., Hu, B., Liu, L., Yang, S., Yang, S., Gong, Z., Lai, P. B. S., & Chen, G. G. (2018) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835918816287 · Cited by 112 · see citing works
Self-citationSun, C., Sun, L., Li, Y., Kang, X., Zhang, S., & Liu, Y. (2013) · Medical Oncology · doi:10.1007/s12032-013-0503-1 · Cited by 110 · see citing works
Chang, W., Lin, R., Yu, J., Chang, W., Fu, C.-H., Lai, A. C., Yu, A. L.-T., & Yu, A. L.-T. (2013) · Breast Cancer Research · doi:10.1186/bcr3423 · Cited by 108 · see citing works
Nanog, as a key cancer stem cell marker in tumor progression
Vasefifar, P., Motafakkerazad, R., Maleki, L. A., Najafi, S., Ghorbaninezhad, F., Najafzadeh, B., Alemohammad, H., Amini, M. A., Baghbanzadeh, A., & Baradaran, B. (2022) · Gene · doi:10.1016/j.gene.2022.146448 · Cited by 106 · see citing works
Regulation of NANOG in cancer cells
Gong, S., Li, Q., Jeter, C. R., Fan, Q., Tang, D. G., & Liu, B. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22340 · Cited by 105 · see citing works
Wang, P., Wan, W., Xiong, S., Feng, H., & Wu, N. (2017) · Cell Death Discovery · doi:10.1038/cddiscovery.2016.105 · Cited by 103 · see citing works
Cancer stem cells and niches: challenges in immunotherapy resistance
Pan, Y., Yuan, C., Zeng, C., Sun, C., Xia, L., Wang, G., Chen, X., Zhang, B., Liu, J., & Ding, Z. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02265-2 · Cited by 110 · see citing works
Self-citationLiu, L., Liu, C., Zhang, Q., Shen, J., Zhang, H., Shan, J., Duan, G., Guo, D., Chen, X., Cheng, J., et al. (2016) · Hepatology · doi:10.1002/hep.28690 · Cited by 102 · see citing works
Self-citationRasti, A., Mehrazma, M., Madjd, Z., Abolhasani, M., Zanjani, L. S., & Asgari, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-30168-4 · Cited by 98 · see citing works
Schulenburg, A., Blatt, K., Cerny‐Reiterer, S., Sadovnik, I., Herrmann, H., Marian, B., Grunt, T. W., Zielinski, C. C., & Valent, P. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-015-0113-9 · Cited by 94 · see citing works
Chang, T., Wu, Y.-C., Chi, C., Su, W.-C., Chang, P., Lee, K.-F., Tung, T.-H., Wang, J., Liu, J., Tung, S., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3274 · Cited by 92 · see citing works
Self-citationStrategies for Isolating and Enriching Cancer Stem Cells: Well Begun Is Half Done
Duan, J., Qiu, W., Xu, S., Wang, B., Ye, X.-Z., Ping, Y., Zhang, X., Bian, X., & Yu, S. (2013) · Stem Cells and Development · doi:10.1089/scd.2012.0613 · Cited by 90 · see citing works
Self-citationMa, L., Liu, J., Liu, L., Duan, G., Wang, Q., Xu, Y., Xia, F., Shan, J., Shen, J., Yang, Z., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2171 · Cited by 91 · see citing works
Self-citationCharacteristics of liver cancer stem cells and clinical correlations
Cheng, Z., Li, X., & Ding, J. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.07.041 · Cited by 86 · see citing works
Heterogeneity of hepatocellular carcinoma contributes to cancer progression
Jeng, K., Chang, C., Jeng, W., Sheen, I., & Jeng, C. (2015) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2015.01.009 · Cited by 87 · see citing works
Cao, J., Zhao, M., Liu, J., Zhang, X., Pei, Y., Wang, J., Yang, X. Y., Shen, B., & Zhang, J. (2019) · Theranostics · doi:10.7150/thno.29271 · Cited by 85 · see citing works
Self-citationSun, C., Sun, L., Jiang, K., Gao, D., Kang, X., Wang, C., Zhang, S., Huang, S., Qin, X. Y., Yan, L., et al. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.02.017 · Cited by 83 · see citing works
Wei, Z., Jia, J., Heng, G., Xu, H., Shan, J., Wang, G., Liu, C., Xia, J., Zhou, H., Wu, M. C., et al. (2019) · Hepatology · doi:10.1002/hep.30622 · Cited by 81 · see citing works
Self-citationLuo, J., Wang, P., Wang, R., Wang, J., Liu, M., Xiong, S., Li, Y., & Cheng, B. (2015) · Oncotarget · doi:10.18632/oncotarget.6672 · Cited by 80 · see citing works
Jin, H., Wang, C., Jin, G., Ruan, H., Gu, D., Wei, L., Wang, H., Wang, N., Arunachalam, E., Zhang, Y., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.045 · Cited by 80 · see citing works
Wang, T., Qin, Z., Wen, L., Guo, Y., Liu, Q., Lei, Z., Pan, W. X., Liu, K., Wang, X., Lai, S., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0095-6 · Cited by 82 · see citing works
Self-citationLiu, C., Liu, L., Shan, J., Shen, J., Xu, Y., Zhang, Q., Yang, Z., Wu, L., Xia, F., Bie, P., et al. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.07.022 · Cited by 79 · see citing works
Self-citationInsulin and cancer: a tangled web
Leitner, B. P., Siebel, S., Akingbesote, N. D., Zhang, X., & Perry, R. J. (2022) · Biochemical Journal · doi:10.1042/bcj20210134 · Cited by 77 · see citing works
Kim, I. G., Kim, S. Y., Choi, S., Lee, J. H., Kim, K. C., & Cho, E. (2013) · Oncogene · doi:10.1038/onc.2013.373 · Cited by 76 · see citing works
Su, L., Luo, Y., Yang, Z., Yang, H. J., Yao, C., Cheng, F., Shan, J., Chen, J., Li, F., Liu, L., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0246 · Cited by 77 · see citing works
Self-citationNgo, M.-H. T., Jeng, H.-Y., Kuo, Y., Nanda, J. D., Brahmadhi, A., Ling, T., Chang, T., & Huang, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041931 · Cited by 75 · see citing works
Liu, Y., Wan, G., Guo, H., Liu, Y., Zhou, P., Wang, H., Wang, D., Zhang, S., Wang, Y., & Zhang, N. (2017) · Nano Research · doi:10.1007/s12274-016-1339-8 · Cited by 75 · see citing works
Kim, J., Lee, H., Park, K.-K., Choi, Y., Nam, J., & Hong, I. (2016) · Oncotarget · doi:10.18632/oncotarget.7954 · Cited by 74 · see citing works
Liu, S., Sun, J. P., Cai, B., Xi, X., Yang, L., Zhang, Z., Feng, Y., & Sun, Y. (2016) · Tumor Biology · doi:10.1007/s13277-016-4848-x · Cited by 73 · see citing works
Sun, L., Beggs, K. M., Borude, P. C., Edwards, G., Bhushan, B., Walesky, C. M., Roy, N., Manley, M. W., Gunewardena, S., O’Neil, M. F., et al. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00027.2015 · Cited by 70 · see citing works
Tang, M., Yang, M., Wu, G., Mo, S., Wu, X., Zhang, S., Yu, R., Hu, Y., Xu, Y., Li, Z., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-0436 · Cited by 70 · see citing works
Self-citationGigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells
Bhummaphan, N., & Pithi Chanvorachote, B. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/836564 · Cited by 68 · see citing works
Zheng, F.-M., Long, Z., Hou, Z.-J., Luo, Y., Xu, L.-Z., Xia, J.-L., Lai, X.-J., Liu, J.-W., Wang, X., Muhammad, K. I., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-1029 · Cited by 65 · see citing works
Self-citationSympathetic and parasympathetic innervation in hepatocellular carcinoma
Zhang, L., Wu, L. L., Huan, H.-B., Chen, X., Wen, X. D., Yang, D. P., & Xia, F. (2017) · Neoplasma · doi:10.4149/neo_2017_605 · Cited by 70 · see citing works
Self-citationTherapy-induced enrichment of cancer stem-like cells in solid human tumors: Where do we stand?
Martins‐Neves, S. R., Cleton-Jansen, A., & Gomes, C. M. F. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.10.011 · Cited by 67 · see citing works
Insights into the Nanog gene: A propeller for stemness in primitive stem cells
Zhang, W., Sui, Y., Ni, J., & Yang, T. (2016) · International Journal of Biological Sciences · doi:10.7150/ijbs.16349 · Cited by 65 · see citing works
PPARδ Mediates the Effect of Dietary Fat in Promoting Colorectal Cancer Metastasis
Wang, D., Fu, L., Wei, J., Xiong, Y., & DuBois, R. N. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0384 · Cited by 64 · see citing works
Kumar, S., Raina, K., Agarwal, C., & Agarwal, R. (2014) · Oncotarget · doi:10.18632/oncotarget.2068 · Cited by 63 · see citing works
The Recent Advances on Liver Cancer Stem Cells: Biomarkers, Separation, and Therapy
Xiao, Y., Lin, M., Jiang, X., Ye, J., Guo, T., Shi, Y., & Bian, X. (2017) · Analytical Cellular Pathology · doi:10.1155/2017/5108653 · Cited by 61 · see citing works
Self-citationEpithelial cell senescence induces pulmonary fibrosis through Nanog-mediated fibroblast activation
Chen, X., Xu, H., Hou, J., Wang, H., Zheng, Y., Li, H., Cai, H., Han, X., & Dai, J. (2019) · Aging · doi:10.18632/aging.102613 · Cited by 60 · see citing works
The oncogenic potential of NANOG: An important cancer induction mediator
Najafzadeh, B., Asadzadeh, Z., azad, R. M., Mokhtarzadeh, A., Baghbanzadeh, A., Alemohammad, H., Shadbad, M. A., Vasefifar, P., Najafi, S., & Baradaran, B. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30063 · Cited by 58 · see citing works
The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells
Kim, S. S., Rait, A. S., Rubab, F., Rao, A. K., Kiritsy, M. C., Pirollo, K. F., Wang, S., Weiner, L. M., & Chang, E. H. (2013) · Molecular Therapy · doi:10.1038/mt.2013.231 · Cited by 56 · see citing works
Maharati, A., & Moghbeli, M. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04434-7 · Cited by 53 · see citing works
Reprogramming and Carcinogenesis—Parallels and Distinctions
Wasik, A. M., Grabarek, J., Pantovic, A., Cieślar‐Pobuda, A., Asgari, H. R., Bundgaard‐Nielsen, C., Rafat, M., Dixon, I., Ghavami, S., & Łoś, M. (2014) · International review of cytology · doi:10.1016/b978-0-12-800097-7.00005-1 · Cited by 54 · see citing works
Park, J. W., Kim, Y., Lee, S.-B., Oh, C. W., Lee, E. J., Ko, J. Y., & Park, J. H. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13180 · Cited by 53 · see citing works
Wei, F., Rong, X., Xie, R., Jia, L.-T., Wang, H., Qin, Y., Chen, L., Shen, H.-F., Lin, X., Yang, J., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5280 · Cited by 53 · see citing works
Hypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells
Prasad, P., Mittal, S. A., Chongtham, J., Mohanty, S., & Srivastava, T. (2017) · Stem Cells · doi:10.1002/stem.2621 · Cited by 53 · see citing works
Therapeutic potential of selective histone deacetylase 3 inhibition
Zhang, L., Chen, Y., Jiang, Q., Song, W., & Zhang, L. J. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.072 · Cited by 51 · see citing works
Notch Signaling in Hepatocellular Carcinoma: Guilty in Association!
Strazzabosco, M., & Fabris, L. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.10.025 · Cited by 52 · see citing works
Lemos, C., Hardt, M. S., Juneja, M., Voss, C., Förster, S., Jerchow, B., Haider, W., Bläker, H., & Stein, U. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1425 · Cited by 52 · see citing works
3D chromatin architecture and epigenetic regulation in cancer stem cells
Feng, Y., Liu, X., & Pauklin, S. (2021) · Protein & Cell · doi:10.1007/s13238-020-00819-2 · Cited by 52 · see citing works
Oncofetal proteins and cancer stem cells
Yan, Q., Fang, X., Li, C., Lan, P., & Guan, X. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220025 · Cited by 51 · see citing works
Lei, T., & Ling, X. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i35.10137 · Cited by 51 · see citing works
Huan, H.-B., Yang, D., Wen, X.-D., Chen, X., Zhang, L. N., Wu, L., Bie, P., & Xia, F. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0559-4 · Cited by 51 · see citing works
Self-citation
- Authors
- Shan, J., Shen, J., Liu, L., Xia, F., Xu, C., Duan, G., Xu, Y., Ma, Q., Yang, Z., Zhang, Q., Ma, L., Liu, J., Xu, S., Yan, X., Bie, P., Cui, Y., Bian, X.-W., & Qian, C.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Qian, Cheng
- ORCID
- Venue
- Hepatology
- Published
- 2012-09
- Volume
- 56
- Issue
- 3
- Pages
- 1004-1014
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1963590109
- Cited by
- 296
- References
- 37
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 8 · 2023: 11 · 2022: 16 · 2021: 22 · 2020: 15 · 2019: 28 · 2018: 24 · 2017: 33 · 2016: 38 · 2015: 40 · 2014: 21 · 2013: 20 · 2012: 5
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (973 Program, 81090423, 2010CB529406, 81101630)
- National Key Research and Development Program of China (2010CB529406)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- Nanog, hepatocellular carcinoma, cancer stem cells, self-renewal, insulin-like growth factor II, IGF1R signaling, pluripotency transcription factors, tumor initiation, drug resistance, sorafenib, cisplatin, tumor invasion and metastasis, stem cell markers
- MeSH terms
- Nanog Homeobox Protein, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Neoplastic Stem Cells, Signal Transduction, Receptor, IGF Type 1, Homeodomain Proteins
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