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| 1 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 2 | Improved cryopreservation of human embryonic stem cells with trehalose显示文摘 | Wu CF Tsung HC Zhang W J Wang Y Lu JH Tang ZY Kuang YP Jin W Cui L Liu W Cao YL | 2006 | 中国生物学文摘2006，20，7： | 2 |
| 3 | cDNA se-quence of human apolipoprotein(a) is homologous to plasminogen显示文摘 | McLean JW Tomlinson JE Kuang W J | 1987 | Nature1987，330，6144： | 1 |
| 4 | Strategies and operat- ing point optimization of statcom control for voltage unbalance miti- gation in three-phase three-wire systems 显示文摘 | KUANG L JINJUN L ZHAOAN W | 2007 | IEEE Transactions on Power Delivery2007，22，1： | 1 |
| 5 | Photosynthetic characteris-tics and tolerance to photo-oxidation of transgenic rice ex-pressing C4 photosynthesis enzymes显示文摘 | Jiao D.M Huang X.Q Li X Chi W Kuang T.Y Zhang Q.D Ku M.S.B and Cho D.H | | 0，，01： | 1 |
| 6 | Protective effects of echinacoside, one of the phenylethanoid glycosides on H202- induced cytotoxicity in PC12 cells 显示文摘 | Kuang R Sun Y Yuan W | 2009 | Planta &led2009，75，14： | 1 |
| 7 | Semiconductor@ Metal-Organic Framework Core-Shell Heterostnwtures: A Case of ZnO@ ZIF-8 Nanorods with Selective Photoeleetrochemical Response显示文摘 | Zhan W Kuang Q Zhou J etal | 2013 | Journal of the American Chemical Society2013，135，5： | 1 |
| 8 | Differential screening and suppression snbtractive hybridazation identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line 显示文摘 | Kuang W W Thompson D A Hoeh R V Weigel R J | 1998 | Nucleic Acids Res1998，26，： | 1 |
| 9 | Relation of HP-GPC profile with mechanical properties of AC mixture 显示文摘 | Kuang W Kim J | 1993 | Materials In Civil Engireering1993，5，4： | 1 |
| 10 | A simple and fast secondary structure prediction method using hidden neural networks 显示文摘 | LIN Kuang SIMOSSIS A V TAYLOR W R HERINGA J | 2005 | Bioinformatics2005，21，2： | 1 |
| 11 | Analysis of temperature-dependent electron-paramagnetie-resonance spectra for S-state ions in MgO 显示文摘 | Kuang X Y Zhang W Badarau I M | 1992 | Phys Rev B1992，45，： | 1 |
| 12 | Semiconductor@metal-organic framework core-shell heterostructures:A case of ZnO@ZIF-8 nanorods with selective photoelectrochemical response显示文摘 | Zhan W W Kuang Q Zhou J Z | 2013 | Journal of the American Chemical Society2013，135，5： | 1 |
| 13 | Phototactic behavior of armand pine bark-weevil, Pissodes punctatus ( Coleoptera : Curculionidae) 显示文摘 | Cheu Y Luo C W Kuang R P | 2013 | Journal of Insect Science2013，3，： | 1 |
| 14 | The dissimilar friction stir lap welding of 1A99 A1 to pure Cu using Zn as filler metal with 'pinless' tool configuration显示文摘 | KUANG B B SHEN Y F CHEN W H YAO X XU H S GAO J C ZHANG J Q | 2015 | Materials & Design2015，68，5： | 1 |
| 15 | Sin显示文摘 | Yan X Z Kuang X Y Mao A J Kuang F G Wang Z H Sheng X W 2013 Acta Phys | 2013 | 62 107402 (in Chinese)2013，，： | 1 |
| 16 | Recognition of Grenvillian volcanic suite in the Shennongjia region and its tectonic significance for the South China Craton 显示文摘 | Qiu X F Ling W L Liu X M Kusky T Berkana W ZhangY H Gao Y J Lu S S Kuang H Liu C X | 2011 | Precambrian Research2011，191，： | 1 |
| 17 | A Ratio-dependent Food Chain Model and Its Applications to Biological Control 显示文摘 | Hsu S B Hwang T W Kuang Y | 2003 | Math Biosci2003，181，1： | 1 |
| 18 | Global analysis of the Michaelis-Menten-type ratio-dependent predator-prey system显示文摘 | Hsu S B Hwang T W Kuang Y | 2001 | J Math Biol2001，42，： | 1 |
| 19 | Vascular endothelial growth factor显示文摘 | Leung DW Cachinaes G Kuang W | 1997 | Endoc Rev1997，18，1： | 1 |
| 20 | The G-712A polymorphism of brain-derived neurotrophic factor is associated with major depression but not schizophrenia显示文摘 | Sun R F Zhu Y S Kuang W J | 2011 | Neurosei Lett2011，489，1： | 1 |
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