Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms.While pursuing this goal,it is also effective in selecting against altered/defective c...Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms.While pursuing this goal,it is also effective in selecting against altered/defective cells with putative(pre)-neoplastic potential,thereby edging the risk of cancer development.The flip side of the coin is that the molecular machinery driving cell competition can also be co-opted by neoplastic cell populations to expand unchecked,outside the boundaries of tissue homeostatic control.This review will focus on information that begins to emerge regarding the role of cell competition in liver physiology and pathology.Liver repopulation by normal transplanted hepatocytes is an interesting field of investigation in this regard.The biological coordinates of this process share many features suggesting that cell competition is a driving force for the clearance of endogenous damaged hepatocytes by normal donor-derived cells,as previously proposed.Intriguing analogies between liver repopulation and carcinogenesis will be briefly discussed and the potential dual role of cell competition,as a barrier or a spur to neoplastic development,will be considered.Cell competition is in essence a cooperative strategy organized at tissue level.One facet of such cooperative attitude is expressed in the elimination of altered cells which may represent a threat to the organismal community.On the other hand,the society of cells can be disrupted by the emergence of selfish clones,exploiting the molecular bar codes of cell competition,thereby paving their way to uncontrolled growth.展开更多
Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced...Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the 'Oxidative Stress' theory has been postulated. In this review, in order to reconsider the significance of 'Oxidative Stress' to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH -dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that 'Oxidative Stress' could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of 'Oxidative Stress' in the carcinogenesis process展开更多
SIRT6 belongs to class III sirtuin family with NAD+-dependent histone deacetylase activities and controls multiple processes including aging,metabolism and inflammation.In recent years,increasing studies showed tumor ...SIRT6 belongs to class III sirtuin family with NAD+-dependent histone deacetylase activities and controls multiple processes including aging,metabolism and inflammation.In recent years,increasing studies showed tumor suppressor role of SIRT6 in HCC development.We established a two-stage DEN followed CC14 induced liver carcinogenesis in the hepatic-specific SIRT6 HKO mice models and found that hepatic S1RT6 deficit significantly promotes liver injury and liver cancer through inhibition of the ERK1/2 pathway.SIRT6 was compensatory up-regulated in mice tumor tissues and human HCC cells and overexpressed SIRT6 inhibits tumor growth both in vitro and in vivo.Taken together,we provide a useful mouse model for delineating the molecular pathways involved in chronic liver diseases and primary liver cancer and suggest that SIRT6 can be a promising target for HCC therapies.展开更多
文摘Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms.While pursuing this goal,it is also effective in selecting against altered/defective cells with putative(pre)-neoplastic potential,thereby edging the risk of cancer development.The flip side of the coin is that the molecular machinery driving cell competition can also be co-opted by neoplastic cell populations to expand unchecked,outside the boundaries of tissue homeostatic control.This review will focus on information that begins to emerge regarding the role of cell competition in liver physiology and pathology.Liver repopulation by normal transplanted hepatocytes is an interesting field of investigation in this regard.The biological coordinates of this process share many features suggesting that cell competition is a driving force for the clearance of endogenous damaged hepatocytes by normal donor-derived cells,as previously proposed.Intriguing analogies between liver repopulation and carcinogenesis will be briefly discussed and the potential dual role of cell competition,as a barrier or a spur to neoplastic development,will be considered.Cell competition is in essence a cooperative strategy organized at tissue level.One facet of such cooperative attitude is expressed in the elimination of altered cells which may represent a threat to the organismal community.On the other hand,the society of cells can be disrupted by the emergence of selfish clones,exploiting the molecular bar codes of cell competition,thereby paving their way to uncontrolled growth.
文摘Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the 'Oxidative Stress' theory has been postulated. In this review, in order to reconsider the significance of 'Oxidative Stress' to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH -dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that 'Oxidative Stress' could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of 'Oxidative Stress' in the carcinogenesis process
基金This study was supported grants from the National Natural Science Foundation of China(No.81902803,81972233)the Overseas Young Talents Project of China,"Innovative and Entrepreneurial Team"(No.(2018)2015)+2 种基金Science and Technology Grant(No.BE2019758)the Natural Science Foundation(No.BK20190657)of Jiangsu Province,Southeast University-Nanjing Medical University Cooperative Research Project(No.2242018K3DN33)Fund of Nanjing Medical University and the China Scholarship Council(No.201906090247).
文摘SIRT6 belongs to class III sirtuin family with NAD+-dependent histone deacetylase activities and controls multiple processes including aging,metabolism and inflammation.In recent years,increasing studies showed tumor suppressor role of SIRT6 in HCC development.We established a two-stage DEN followed CC14 induced liver carcinogenesis in the hepatic-specific SIRT6 HKO mice models and found that hepatic S1RT6 deficit significantly promotes liver injury and liver cancer through inhibition of the ERK1/2 pathway.SIRT6 was compensatory up-regulated in mice tumor tissues and human HCC cells and overexpressed SIRT6 inhibits tumor growth both in vitro and in vivo.Taken together,we provide a useful mouse model for delineating the molecular pathways involved in chronic liver diseases and primary liver cancer and suggest that SIRT6 can be a promising target for HCC therapies.