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Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Zoological Research 2024年第3期45卷 506-517页

作者： Xilei Peng Haonan Dong Lixing Zhang Suling Liu Fudan University Shanghai Cancer center&Institutes of Biomedical Sciences/State Key Laboratory of Genetic Engineering/Cancer Institutes/Department of Oncology/Key Laboratory of Breast Cancer in Shanghai/Shanghai Key Laboratory of Medical Epigenetics/Shanghai Key Laboratory of Radiation Oncology/International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology/Shanghai Medical College/Fudan UniversityShanghai 200032China

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

关键词： Breast cancer Metastasis Cancer stem cell Ecosystem Tumor microenvironment Mouse model

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Microplastic Can Decrease Enzyme Activities and microbes in Soil

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Open Journal of Soil Science 2024年第1期14卷 1-12页

作者： Tazeen Fatima Khan Abdul Halim Farhad Sikder Department of Soil Water and Environment University of Dhaka Dhaka Bangladesh center for Environmental and Geographic Information Services Dhaka Bangladesh

An in vitro study was conducted to investigate the impacts of microplastics on enzyme activities and soil bacteria. The study included four different treatments of microplastics including a control. Different levels of microplastics were applied to the soil ranging from 0% to 5%, to assess the impacts of microplastics on soil enzymes and subsequent soil bacteria. After 30 days of incubation, the soil samples were collected and growth parameters of bacteria were assessed. Activities of β-glucosidase, urease and dehydrogenase enzymes were also determined. Our results showed that the presence of microplastics in the soil significantly reduced bacterial population together with bacterial strains. The activities of β-glucosidase, urease and dehydrogenase enzymes were reduced significantly to approximately 32%, 40% and 50% in microplastics treated soils respectively. Concentration of microplastic has a role to play towards this direction;the higher the concentration of microplastic the greater is the impact on enzymes and soil bacteria. The present study on the microbial soil health vis-à-vis microplastic application indicates that the material can have negative effect on the soil bacterial population of and thus ultimately may jeopardize soil health and crop production.

关键词： Microplastic Concentration Enzyme Activity Bacteria Crop Production

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Characterization of C_(30) carotenoid and identification of its biosynthetic gene cluster in Methylobacterium extorquens AM1

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Synthetic and Systems Biotechnology 2023年第3期8卷 527-535页

作者： Xu-Hua Mo Yu-Man Sun Yu-Xing Bi Yan Zhao Gui-Hong Yu Ling-ling Tan Song Yang School of Life Sciences Qingdao Agricultural University700 Changcheng RoadQingdaoShandong266109China Shandong Province Key Laboratory of Applied Mycology Qingdao Agricultural University700 Changcheng RoadQingdaoShandong266109China Qingdao International center on microbes Utilizing Biogas Qingdao Agricultural UniversityQingdaoShandong ProvinceChina

Methylobacterium species,the representative bacteria distributed in phyllosphere region of plants,often synthesize carotenoids to resist harmful UV radiations.Methylobacterium extorquens is known to produce a carotenoid pigment and recent research revealed that this carotenoid has a C_(30) backbone.However,its exact structure remains unknown.In the present study,the carotenoid produced by M.extorquens AM1 was isolated and its structure was determined as 4-[2-O-11Z-octadecenoyl-β-glucopyranosyl]-4,4′-diapolycopenedioc acid(1),a glycosylated C_(30) carotenoid.Furthermore,the genes related to the C_(30)carotenoid synthesis were investigated.Squalene,the precursor of the C_(30) carotenoid,is synthesized by the co-occurrence of META1p1815,META1p1816 and META1p1817.Further overexpression of the genes related to squalene synthesis improved the titer of carotenoid 1.By using gene deletion and gene complementation experiments,the glycosyltransferase META1p3663 and acyltransferase META1p3664 were firstly confirmed to catalyze the tailoring steps from 4,4′-diapolycopene-4,4′-dioic acid to carotenoid 1.In conclusion,the structure and biosynthetic genes of carotenoid 1 produced by M.extorquens AM1 were firstly characterized in this work,which shed lights on engineering M.extorquens AM1 for producing carotenoid 1 in high yield.

关键词： C_(30)carotenoid Methylobacterium extorquens Biosynthetic gene cluster Glycosyltransferase Acyltransferase

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Potential transformation of organic matter by microbes in cryoconite,Tibetan Plateau

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Science China Earth Sciences 2024年第6期67卷 1978-1989页

作者： Bixi GUO Yongqin LIU Kevin Xu ZHONG Quan SHI Chen HE Qiang ZHENG Ruanhong CAI State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China center for the Pan-Third Pole Environment Lanzhou UniversityLanzhou 730000China Department of Earth Oceanand Atmospheric SciencesUniversity of British ColumbiaVancouverBC V6T 1Z4Canada State Key Laboratory of Heavy Oil Processing Petroleum Molecules Engineering Center(PMEC)China University of PetroleumBeijing 102249China State Key Laboratory for Marine Environmental Science Collage of Ocean and Earth SciencesXiamen UniversityXiamen 361102China Fujian Key Laboratory of Marine Carbon Sequestration Xiamen UniversityXiamen 361005China

Microorganisms play an essential role in the glacier carbon cycle;how they transform organic matter in mountain glacial cryoconite remains to be studied.Here,we applied ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR MS)and deep sequencing of 16S rRNA gene,to investigate the temporal microbial transformation of dissolved organic matter(DOM)of the Tibetan Plateau cryoconite.During the 60-day incubation,we found that DOM in cryoconite underwent a three-stage transformation,with decreasing bioavailability over time.The microbial community did not change much in the first week while degrading DOM molecules that were associated with higher H/C_(wa)and lower O/C_(wa).During days 15-30,DOM composition remained stable while microbial diversity increased.By day 60,the DOM was microbially converted into a higher state of recalcitrance,with higher values of aromatic index,O/C_(wa),and lower H/C_(wa),which contained molecules containing more heteroatoms.Cooperation among various microbial taxa,like Cyanobacteria,Bacteroidota,Gammaproteobacteria,Firmicutes,and Actinobacteriota,drove the DOM transformation in cryoconite.This study sheds light on the in-situ transformation of DOM composition meditated by microbial populations in cryoconite at a temporal scale,providing new insights into understanding the microbial roles in the glacier organic carbon transformation.

关键词： Cryoconite Dissolved organic matter Biodegradation Microbial community Temporal variation

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Stem cell retrograde:A new reason why colorectal cancer is more common than small intestinal cancer?

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The Innovation 2023年第2期4卷 7-8页

作者： Rongkang Tang Philippe Joseph Sansonetti Yi-Zhou Gao the center for microbes Development and HealthInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China Unitéde Pathogénie Microbienne Moléculaire Institut Pasteur75015 ParisFrance

The intestine is exposed to a dynamic internal environment that is full of phys-iological stimuli and has a high risk of being invaded by pathogenic factors.It has dynamic fold units referred to as crypts that are composed of epithelial cells to ward off potential damage from gut lumen.Apart from the crypt,the small intes-tine(SI)contains villi that is covered by functionally differentiated cells,such as absorptive epithelial cells to maintain nutrient exchange with luminal environ-ments.Intestinal stem cells(ISCs)are responsible for self-repair mechanisms of the intestine epithelium.They have the ability to differentiate and proliferate,are well protected,and are located at the bottom of the intestinal crypt structure(Figure 1A).

关键词： intestine epithelium colorectal

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The secretory Candida effector Sce1 licenses fungal virulence by masking the immunogenicβ-1,3-glucan and promoting apoptosis of the host cells

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微生物(英文) 2023年第2期2卷 159-177页

作者： Hongyu Wu Li Wang Wenjuan Wang Zhugui Shao Xin-Ming Jia Hui Xiao Jiangye Chen State Key Laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina the center for microbes Development and HealthInstitut Pasteur of ShanghaiChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina Clinical Medicine Scientific and Technical Innovation center Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Biomedical SciencesShandong UniversityJinanChina

Candida albicans deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence.However,the intricate interactions between the fungus and the host remain poorly understood,and a comprehensive inventory of fungal virulence factors has yet to be established.In this study,we identified a C.albicans secretory effector protein Sce1,whose induction and secretion are associated with vagina‐simulative conditions and chlamydospore formation.Sequence alignment showed that Sce1 belongs to a Pir family in C.albicans,which is conserved across several fungi and primarily characterized as aβ‐glucan binding protein in the Saccharomyces cerevisiae.Mechanically,Sce1 is primarily localized to the cell wall in a cleaved form as an alkali‐labileβ‐1,3‐glucan binding protein and plays a role in maskingβ‐glucan in acidic environments and chlamydospores,a feature that might underline C.albicans'ability to evade host immunity.Further,a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow‐derived macrophages infected with chlamydospores.This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases‐8/9‐dependent apoptosis in various host cells.Correspondingly,genetic deletion of SCE1 led to dampened vaginal colonization of C.albicans and diminished fungal virulence during systemic infection.The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus–host interactions and C.albicans pathogenesis.

关键词： apoptosis Candida albicans effector immune evasion β-glucan

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TAK1 Deficiency in Macrophages Increases Host Susceptibility to Leishmania Infection

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感染微生物与疾病(英文) 2023年第3期5卷 127-136页

作者： Xiankai Cao Kossiwa C.Kokou Shi Yu Mengdan Chen Junling Niu HervéLecoeur Eric Prina Gerald F.Späth Guangxun Meng the center for microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyUniversity of Chinese Academy of SciencesShanghaiChina Institute Pasteur Paris City UniversityINSERM U1201Molecular Parasitology and Signalling UnitParisFrance Pasteurien College Soochow UniversitySuzhouChina Nanjing Advanced Academy of Life and Health NanjingChina.

Leishmania parasites mainly infect macrophages and may cause severe immunopathologies in their host,which are called leishman-iases.In the current work,we infected human and mouse macrophages in vitro with Leishmania major,an etiological agent of cu-taneous leishmaniasis,and found that inhibition or deletion of the transforming growth factorβ–activated kinase 1(TAK1)gene re-sulted in increased parasite loads.In vivo,following a challenge with L.major,mice with a macrophage-specific deletion of TAK1 showed increased clinical signs and higher parasite loads compared with wild-type controls.TAK1 deficiency in mouse macro-phages led to biased Th2 cell responses during the acute stage of infection,characterized by a decrease in interferon-γexpression,and increased expression of IL-4,IL-5 and IL-10.Finally,we found that,in the late stage of L.major infection,excessive Th2-related cytokines led to high arginase 1 expression in mouse tissues and a significant reduction of NO production both locally and system-ically,resulting in compromised control of Leishmania.These findings suggest that TAK1 plays a vital role in host resistance to Leish-mania infection.

关键词： TAK1 macrophage Leishmania major arginase 1 nitric oxide

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Identification and expression analysis of sugar transporter family genes reveal the role of ZmSTP2 and ZmSTP20 in maize disease resistance

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Journal of Integrative Agriculture 2023年第11期22卷 3458-3473页

作者： MA Yu-xin ZHOU Zhi-jun CAO Hong-zhe ZHOU Fan SI He-long ZANG Jin-ping XING Ji-hong ZHANG Kang DONG Jin-gao State Key Laboratory of North China Crop Improvement and Regulation Hebei Agricultural UniversityBaoding 071000P.R.China Hebei Key Laboratory of Plant Physiology and Molecular Pathology Hebei Agricultural UniversityBaoding 071000P.R.China Hebei Bioinformatic Utilization and Technological Innovation center for Agricultural microbes Hebei Agricultural UniversityBaoding 071000P.R.China Experimental Training center of Hebei Agricultural University Hebei Agricultural UniversityBaoding 071000P.R.China

Sugar is an indispensable source of energy for plant growth and development, and it requires the participation of sugar transporter proteins(STPs) for crossing the hydrophobic barrier in plants. Here, we systematically identified the genes encoding sugar transporters in the genome of maize(Zea mays L.), analyzed their expression patterns under different conditions, and determined their functions in disease resistance. The results showed that the mazie sugar transporter family contained 24 members, all of which were predicted to be distributed on the cell membrane and had a highly conserved transmembrane transport domain. The tissue-specific expression of the maize sugar transporter genes was analyzed, and the expression level of these genes was found to be significantly different in different tissues. The analysis of biotic and abiotic stress data showed that the expression levels of the sugar transporter genes changed significantly under different stress factors. The expression levels of Zm STP2 and Zm STP20 continued to increase following Fusarium graminearum infection. By performing disease resistance analysis of zmstp2 and zmstp20 mutants, we found that after inoculation with Cochliobolus carbonum, Setosphaeria turcica, Cochliobolus heterostrophus, and F. graminearum, the lesion area of the mutants was significantly higher than that of the wild-type B73 plant. In this study, the genes encoding sugar transporters in maize were systematically identified and analyzed at the whole genome level. The expression patterns of the sugar transporter-encoding genes in different tissues of maize and under biotic and abiotic stresses were revealed, which laid an important theoretical foundation for further elucidation of their functions.

关键词： maize sugar transporter gene expression disease resistance

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cFLIPS regulates alternative NLRP3 inflammasome activation in human monocytes

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Cellular & Molecular Immunology 2023年第10期20卷 1203-1215页

作者： Yuhui Gao Shi Yu Mengdan Chen Xun Wang Lei Pan Bin Wei Guangxun Meng School of Life Sciences Shanghai UniversityShanghai200444China the center for microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyUniversity of Chinese Academy of SciencesShanghai200031China Shanghai Blood center Shanghai200051China Pasteurien College Soochow UniversitySuzhou215006JiangsuChina Nanjing Advanced Academy of Life and Health Nanjing211135JiangsuChina Department of Basic Research Guangzhou LaboratoryGuangzhou International Bio-lslandGuangzhou 510o05 GuangdongChina

The innate immune responses,including inflammasome activation,are paramount for host defense against pathogen infection.In contrast to canonical and noncanonical inflammasome activation,in this study,heat-killed gram-negative bacteria(HK bacteria)were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes,and they caused a moderate amount of IL-1βto be released from cells.Time course experiments showed that this alternative inflammasome response was finished within a few hours.Further analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP(cFLIPs),which was activated by NF-κB.In contrast,overexpressed cFLIPS,but not overexpressed cFLIPL,inhibited the activation of caspase-8 and the release of IL-1βin response to HK bacteria infection in human monocytes.Furthermore,we demonstrated that TAK1 activity mediated the expression of cFLIPs and was upstream and essential for the caspase-8 cleavage induced by HK bacteria in human monocytes.The functional specificity of cFLIPs and TAK1 revealed unique responses of human monocytes to a noninvasive pathogen,providing novel insights into an alternative regulatory pathway of NLRP3 inflammasome activation.

关键词： cFLIPS gram-negative bacteria NLRP3 inflammasome human monocyte

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Decoding the complexity of metastasis

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Cancer Biology & Medicine 2022年第3期19卷 284-288页

作者： Yingcheng Wu Tiancheng Zhang Xiaoming Zhang Qiang Gao Department of Liver Surgery and Transplantation Key Laboratory of Carcinogenesis and Cancer Invasion(Ministry of Education)Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China the center for microbes Development and HealthKey Laboratory of Molecular Virology and ImmunologyInstitute Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China Key Laboratory of Medical Epigenetics and Metabolism Institutes of Biomedical SciencesFudan UniversityShanghai 200032China State Key Laboratory of Genetic Engineering Fudan UniversityShanghai 200433China

Cancer metastasis remains one of the most confounding questions in oncology1,2.Although current cutting-edge techniques enable very early detection of tumors,profiling whether a tumor has already begun to spread and where it has attempted to colonize remains a major hurdle.Indeed,metastatic seeding events exhibit remarkable temporal and spatial heterogeneity,wherein the origin(primary site)and destination(metastatic site)are highly dynamic.For example,liver metastasis is particularly common and remains a leading cause of mortality3.

关键词： metastasis mortality founding

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