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Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

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World Journal of Gastroenterology 2019年第32期25卷 4715-4726页

作者： Ran-Xu Zhu alfred sze lok cheng Henry Lik Yuen Chan Dong-Ye Yang Wai-Kay Seto Department of Gastroenterology and Hepatology The University of Hong Kong–Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell ***2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor ***,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully *** To investigate the function and mechanism of GAS2 in *** GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western *** proliferation was analyzed by counting,MTS,and colony formation *** cycle analysis was performed by flow *** apoptosis was investigated by Annexin V apoptosis assay and western *** GAS2 protein expression was lower in HCC than in normal *** of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide *** expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of *** the clinic specimen,GAS2 was downregulated in more than 60%of *** average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.

关键词： Growth arrest-specific gene 2 Cell cycle Apoptosis Hepatocellular carcinoma p53-dependent signaling pathway

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： 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 School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,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 *** 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)*** 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,***,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 ***,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 *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

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World Journal of Gastroenterology 2014年第14期20卷 3847-3857页

作者： Andy Hin-Fung Tsang Ka-Ho cheng Apple Siu-Ping Wong Simon Siu-Man Ng Brigette Buig-Yue Ma Charles Ming-lok Chan Nancy Bo-Yin Tsui Lawrence Wing-Chi Chan Benjamin Yat-Ming Yung sze-Chuen Cesar Wong Department of Health Technology and Informatics Faculty of Health and Social SciencesHong Kong Polytechnic University Department of Surgery Prince of Wales Hospital State Key Laboratory in Oncology in South China Sir Y K Pao Centre for CancerDepartment of Clinical OncologyHong Kong Cancer Institute and Prince of Wales HospitalThe Chinese University of Hong Kong

Colorectal cancer(CRC)is one of the most prevalent cancers in developed *** the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or *** CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the *** occult blood test is a widely used non-invasive screening tool for *** fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the *** dysregulations have been found to play an important role in CRC *** better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for *** this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were *** review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.

关键词： Colorectal cancer Colorectal adenoma Molecular diagnostics Fecal occult blood test Non-invasive

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