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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 | Effects and mechanisms of nonylphenol on corticosterone release in rat zona fasciculata-reticularis cells 显示文摘 | CHANG L L ALFRED WUN W S WANG P S | 2010 | Toxicol Sci2010，118，2： | 1 |
| 3 | Diversity of uncultured microorganisms associated with the seagrass Halophila stipulacea estimated by restriction fragment length polymorphism analysis of PCR-amplified 16S rRNA显示文摘 | Siefan W Walter A Alfred P | 1996 | Genes Appl Environ Microbiol1996，62，： | 1 |
| 4 | Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview显示文摘 | Alfred H Schinkel Johan W Jonker | 2003 | Advanced Drug Delivery Reviews2003，，1： | 1 |
| 5 | The future of peer-to-peer computing显示文摘 | Alfred W Loo | 2003 | Communications of the ACM2003，46，9： | 1 |
| 6 | Why Are We Doing This: Clinician Helplessness in the Face of Suf- fering 显示文摘 | Back Anthony L Rushton Cynda H Kaszniak Alfred W Halifax Joan S | 2015 | Journal of Palliative Medicine2015，15，1： | 1 |
| 7 | A new approach to the differential quadrature method for fourth-order equation显示文摘 | Alfred G Bert C W | 1997 | Internat J Numer Methods Engrg1997，40，11： | 1 |
| 8 | Is combined chemotherapy and radiation therapy equally effective as surgical resection in localized esophageal carcinoma显示文摘 | Alexander C Alfred W | 1999 | Int J Radiat Oncol Biol Phys1999，45，： | 1 |
| 9 | Acquisition of timing and Doppler-shift in a direct-sequence spread-spectrum system显示文摘 | Alfred W Fuxjaeger Ronald A Iltis | 1994 | IEEE Trans on Commun1994，42，10： | 1 |
| 10 | Is combined chemotherapy and radiation therapy equally effective as surgical resection in localized esophageal carcinoma显示文摘 | Alexander C Alfred W | 1999 | international Journal of Radiation Oncology Biology Physics1999，45，2： | 1 |
| 11 | Electrochemical-enzymatic analysis of blood glucose and lactate 显示文摘 | DAVID L W ALFRED R D J ALEXANDER K | 1970 | Anal Chem1970，42，1： | 1 |
| 12 | The effect of soy protein additions on the reactivity and formadehyde emissions of ureaformaldehyde adhesive resins显示文摘 | Linda F Lorenz Anthony H Conner Alfred W Christiansen | 1999 | Forest Products Journal1999，49，： | 1 |
| 13 | Crosby,The Past and Present of Environmental History显示文摘 | Alfred W | 1995 | American Historical Review1995，100，： | 1 |
| 14 | Vibration analysis of horizontally curved beams with warping using DQM显示文摘 | Kijun K Charles W B Alfred Q S | 1996 | Journal of Structural Engineering1996，122，6： | 1 |
| 15 | Separation of racemates into their optically active components by means of addition compounds 显示文摘 | RICHARD W ALFRED A | 1932 | Monatsh Chem1932，59，： | 1 |
| 16 | Is combined chemotherapy and radiationtherapy equally effective as surgical resection in localized esophagealcarcinoma显示文摘 | Alexander C Alfred W | 1999 | Int J Radiat Oncol Biol Phys1999，550，2： | 1 |
| 17 | Estrogen receptor alpha(ER-a) and beta (ER- mRN As in normal ovary, ovarian serous cys- tadenoeareinoma and ovarian cancer cell lines:Dow regulation of ER-显示文摘 | Alfred W Brandenberder Meng Kian Tee Robert B Jaffe | 1998 | Journal of Clinical Endocrinology and Metabolism1998，83，3： | 1 |
| 18 | NASA radar altimeter for the TOPEX/POSEIDON project显示文摘 | Alfred R Zieger David W Hancock George S Hayne Craig L Purdy | 1991 | Proceedings of the IEEE1991，79，6： | 1 |
| 19 | Decontamination of 2-chloroethyl Ethylsulfide Using Titanate Nanoscrolls显示文摘 | ALFRED K GEORGE W W Harsha K | 2005 | Chemical Physics Letters2005，411，： | 1 |
| 20 | Temperature- dependent mechanical and long crack behavior of zirconium diboride silicon carbide composite 显示文摘 | Marc W B Robert P A Alfred F T | 2012 | Journal of the European Ceramic Society2012，32，12： | 1 |
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