Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as ...Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as well as the immune,nervous and endocrine systems,to construct a self-sustainable tumor ecosystem.With increasing evidence for the systemic tumor-host interplay,we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has come.Revolving around the tumor ecosystem scoped as different hierarchies of primary,regional,distal and systemic onco-spheres,we comprehensively review the tumor-host interaction among cancer cells and their local microenvironment,distant organ niches,immune,nervous and endocrine systems,highlighting material and energy flow with tumor ecological homeostasis as an internal driving force.We also substantiate the knowledge of visualizing,modelling and subtyping this dynamically intertwined networkwith recent technological advances,and discuss ecologically rational strategies formore effective cancer therapies.展开更多
Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely...Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.展开更多
A highly dynamic development process exits within the epithelia of mammary gland,featuring morphogenetic variation during puberty,pregnancy,lactation,and regression.The identification of mammary stem cells(MaSCs)via l...A highly dynamic development process exits within the epithelia of mammary gland,featuring morphogenetic variation during puberty,pregnancy,lactation,and regression.The identification of mammary stem cells(MaSCs)via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia.A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation.Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes,it still lacks experimental proofs whether MaSCs,the most primitive cells,are the‘seeds’of malignant transformation during most,if not all,tumorigenesis in the breast.Here,we review current knowledge of mammary epithelial hierarchy,highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells(BCSCs)along with their key molecular regulators in organ development and cancer evolution.Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer(BrCa).展开更多
基金Natural Science Foundation of China,Grant/Award Numbers:81621004,81930081Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515010238China Postdoctoral Science Foundation,Grant/Award Numbers:2020M683106,2021T140763。
文摘Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as well as the immune,nervous and endocrine systems,to construct a self-sustainable tumor ecosystem.With increasing evidence for the systemic tumor-host interplay,we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has come.Revolving around the tumor ecosystem scoped as different hierarchies of primary,regional,distal and systemic onco-spheres,we comprehensively review the tumor-host interaction among cancer cells and their local microenvironment,distant organ niches,immune,nervous and endocrine systems,highlighting material and energy flow with tumor ecological homeostasis as an internal driving force.We also substantiate the knowledge of visualizing,modelling and subtyping this dynamically intertwined networkwith recent technological advances,and discuss ecologically rational strategies formore effective cancer therapies.
基金supported by the National Natural Science Foundation of China(82173054,82222029,82203085)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020048,2022B1515020101,China)Guangzhou Science,Technology and Innovation Commission(202102010148,China).
文摘Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.
基金This work was supported by grants from the Natural Science Foundation of China(81472468,81490750,81230060,81442009,81472467,81272894,81372819)Science Foundation of Guangdong Province(2016A030306023,2014A030313094,S2012030006287,2014A030313175)973(SQ2015CB050449)Projects from Ministry of Science and Technology of China.
文摘A highly dynamic development process exits within the epithelia of mammary gland,featuring morphogenetic variation during puberty,pregnancy,lactation,and regression.The identification of mammary stem cells(MaSCs)via lineage-tracing studies has substantiated a hierarchical organization of the mammary epithelia.A single MaSC is capable of reconstituting the entirely functional mammary gland upon orthotopic transplantation.Although different mammary cell subpopulations can be candidate cells-of-origin for distinct breast tumor subtypes,it still lacks experimental proofs whether MaSCs,the most primitive cells,are the‘seeds’of malignant transformation during most,if not all,tumorigenesis in the breast.Here,we review current knowledge of mammary epithelial hierarchy,highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells(BCSCs)along with their key molecular regulators in organ development and cancer evolution.Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer(BrCa).
