TPO-Induced Metabolic Reprogramming Drives Liver Metastasis of Colorectal Cancer CD110+ Tumor-Initiating Cells
作者： ZhengMing Wu , Dong Wei , WenChao Gao , YuTing Xu , ZhiQian Hu
DOI: 10.1016/J.STEM.2015.05.016
关键词: LRP6 、 Colorectal cancer 、 Biology 、 Tyrosine phosphorylation 、 Wnt signaling pathway 、 Thrombopoietin 、 Metastasis 、 Chromatin 、 Cancer research 、 Receptor
摘要: Liver metastasis is a leading cause of death in patients with colorectal cancer. We previously found that cancer tumor-initiating cells (TICs) expressing CD110, the thrombopoietin (TPO)-binding receptor, mediate liver metastasis. Here, we show TPO promotes CD110+ TICs to by activating lysine degradation. Lysine catabolism generates acetyl-CoA, which used p300-dependent LRP6 acetylation. This triggers tyrosine phosphorylation LRP6, ultimately Wnt signaling promote self-renewal of CD110+ TICs. also glutamate, modulates redox status colonization and drug resistance. Mechanistically, TPO-mediated induction c-myc orchestrates recruitment chromatin modifiers regulate metabolic gene expression. Our findings, therefore, establish as component physiological environment critical for liver.
core.ac.uk
sci-hub.se 参考文章(38)
P G Richman, A Meister, Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. Journal of Biological Chemistry. ,vol. 250, pp. 1422- 1426 ,(1975) , 10.1016/S0021-9258(19)41830-9
Thomas G Martin III, Kenneth A Somberg, Y Gloria Meng, Robert L Cohen, Christian A Heid, Frederic J de Sauvage, Marc A Shuman, Thrombopoietin Levels in Patients with Cirrhosis before and after Orthotopic Liver Transplantation Annals of Internal Medicine. ,vol. 127, pp. 285- 288 ,(1997) , 10.7326/0003-4819-127-4-199708150-00005
K. Skena, J. Locker, S. C. Watkins, D. B. Stolz, H. Waller, J. M. Jessup, K. H. Edmiston, P. Battle, Reactive nitrogen and oxygen radicals formed during hepatic ischemia-reperfusion kill weakly metastatic colorectal cancer cells. Cancer Research. ,vol. 59, pp. 1825- 1829 ,(1999)
C Niehrs, Function and biological roles of the Dickkopf family of Wnt modulators Oncogene. ,vol. 25, pp. 7469- 7481 ,(2006) , 10.1038/SJ.ONC.1210054
Bradley E. Bernstein, Tarjei S. Mikkelsen, Xiaohui Xie, Michael Kamal, Dana J. Huebert, James Cuff, Ben Fry, Alex Meissner, Marius Wernig, Kathrin Plath, Rudolf Jaenisch, Alexandre Wagschal, Robert Feil, Stuart L. Schreiber, Eric S. Lander, A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells Cell. ,vol. 125, pp. 315- 326 ,(2006) , 10.1016/J.CELL.2006.02.041
Tomek Swigut, Joanna Wysocka, H3K27 Demethylases, at Long Last Cell. ,vol. 131, pp. 29- 32 ,(2007) , 10.1016/J.CELL.2007.09.026
Guo-Zhong Tao, Nadja Lehwald, Kyu Yun Jang, Joy Baek, Baohui Xu, M. Bishr Omary, Karl G. Sylvester, Wnt/β-Catenin Signaling Protects Mouse Liver against Oxidative Stress-induced Apoptosis through the Inhibition of Forkhead Transcription Factor FoxO3 Journal of Biological Chemistry. ,vol. 288, pp. 17214- 17224 ,(2013) , 10.1074/JBC.M112.445965
Feng-Shan Wang, Zi-Gong Shao, Jia-Lin Zhang, Yong-Feng Liu, Colorectal liver metastases rarely occur in patients with chronic hepatitis virus infection. Hepato-gastroenterology. ,vol. 59, pp. 1390- 1392 ,(2011) , 10.5754/HGE11747
Vasily V Ogryzko, R.Louis Schiltz, Valya Russanova, Bruce H Howard, Yoshihiro Nakatani, The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases Cell. ,vol. 87, pp. 953- 959 ,(1996) , 10.1016/S0092-8674(00)82001-2
Ioannis A Voutsadakis, Thrombocytosis as a prognostic marker in gastrointestinal cancers. World Journal of Gastrointestinal Oncology. ,vol. 6, pp. 34- 40 ,(2014) , 10.4251/WJGO.V6.I2.34