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)cons...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.展开更多
In recent years,the area dedicated to cotton cultivation in eastern Henan Province has experienced a continuous decline.Developing efficient multi-cropping systems for cotton and increasing the multiple cropping index...In recent years,the area dedicated to cotton cultivation in eastern Henan Province has experienced a continuous decline.Developing efficient multi-cropping systems for cotton and increasing the multiple cropping index represent effective strategies to stabilize the cotton planting area and enhance the income of cotton farmers.This paper presents an overview of intercropping systems and the benefits associated with cotton rotation and intercropping practices.Specifically,it discusses the"early maturing cotton-wheat"rotation system,the"cotton-watermelon"intercropping system,the"cotton-Dutch bean"intercropping system,and the"early maturing cotton-peanut-garlic"intercropping system.展开更多
Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair ...Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair damaged DNA or disrupting cells when DNA cannot be repaired.When BRCA1 is mutated and cannot function and therefore the damaged DNA cannot be repaired展开更多
Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression.However,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail.Here,we ...Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression.However,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail.Here,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy.ETBF,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance.Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein.NOD1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs.NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.展开更多
Our previous studies have showed that C-C motif chemokine ligand 20(CCL20)advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell(BCSC)self-renewal....Our previous studies have showed that C-C motif chemokine ligand 20(CCL20)advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell(BCSC)self-renewal.However,it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment(TME).Here,we observed that polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors.Mechanistically,CCL20 activated the differentiation of granulocyte-monocyte progenitors(GMPs)via its receptor C-C motif chemokine receptor 6(CCR6)leading to the PMN-MDSC expansion.PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors(CCL20-modulated PMN-MDSCs)secreted amounts of C-X-C motif chemokine ligand 2(CXCL2)and increased ALDH+BCSCs via activating CXCR2/NOTCH1/HEY1 signaling pathway.Furthermore,C-X-C motif chemokine receptor 2(CXCR2)antagonist SB225002 enhanced the docetaxel(DTX)effects on tumor growth by decreasing BCSCs in CCL20high-expressing tumors.These findings elucidated how CCL20 modulated the TME to promote cancer development,indicating a new therapeutic strategy by interfering with the interaction between PMN-MDSCs and BCSCs in breast cancer,especially in CCL20high-expressing breast cancer.展开更多
Triple-negative breast cancer(TNBC)is a nasty disease with extremely high malignancy and poor prognosis.Annexin A3(ANXA3)is a potential prognosis biomarker,displaying an excellent correlation of ANXA3 overexpression w...Triple-negative breast cancer(TNBC)is a nasty disease with extremely high malignancy and poor prognosis.Annexin A3(ANXA3)is a potential prognosis biomarker,displaying an excellent correlation of ANXA3 overexpression with patients'poor prognosis.Silencing the expression of ANXA3effectively inhibits the proliferation and metastasis of TNBC,suggesting that ANXA3 can be a promising therapeutic target to treat TNBC.Herein,we report a first-in-class ANXA3-targeted small molecule(R)-SL18,which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells.(R)-SL18 directly bound to ANXA3 and increased its ubiquitination,thereby inducing ANXA3 degradation with moderate family selectivity.Importantly,(R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model.Furthermore,(R)-SL18 could reduce theβ-catenin level,and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells.Collectively,our data suggested that targeting degradation of ANXA3 by(R)-SL18 possesses the potential to treat TNBC.展开更多
Cancer stem cells （CSCs）, a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and rel...Cancer stem cells （CSCs）, a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA （ncRNA） including microRNAs and long non-coding RNAs （IncRNAs）, and histone-modifiers, such as let- 7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, IncRNAs and histone- modifiers especially Polycomb family proteins in regulating breast cancer stem cells （BCSCs）.展开更多
Folate metabolism plays an essential role in tumor development.Various cancers display therapeutic response to reagents targeting key enzymes of the folate cycle,but obtain chemoresistance later.Therefore,novel target...Folate metabolism plays an essential role in tumor development.Various cancers display therapeutic response to reagents targeting key enzymes of the folate cycle,but obtain chemoresistance later.Therefore,novel targets in folate metabolism are highly demanded.Methylenetetrahydrofolate dehydrogenase/methylenetetrahydrofolate cyclohydrolase 2(MTHFD2)is one of the key enzymes in folate metabolism and its expression is highly increased in mutiple human cancers.However,the underlying mechanism that regulates MTHFD2 expression remains unknown.Here,we elucidate that SIRT4 deacetylates the conserved lysine 50(K50)residue in MTHFD2.K50 deacetylation destabilizes MTHFD2 by elevating cullin 3 E3 ligase-mediated proteasomal degradation in response to stressful stimuli of folate deprivation,leading to suppression of nicotinamide adenine dinucleotide phosphate production in tumor cells and accumulation of intracellular reactive oxygen species,which in turn inhibits the growth of breast cancer cells.Collectively,our study reveals that SIRT4 senses folate availability to control MTHFD2 K50 acetylation and its protein stability,bridging nutrient/folate stress and cellular redox to act on cancer cell growth.展开更多
Hydrodynamic, physical, and biochemical processes in the Baiyangdian Lake water environment were analyzed comprehensively. An eutrophication eco- dynamics model including the effects of reed resistance on flow was cou...Hydrodynamic, physical, and biochemical processes in the Baiyangdian Lake water environment were analyzed comprehensively. An eutrophication eco- dynamics model including the effects of reed resistance on flow was coupled with the hydrodynamics governing equations. An improvement on the Water Quality Analysis Simulation Program （WASP, a modeling system intro- duced by the US Environmental Protection Agency） is established, which uses the zooplankton kinetic equation. The model simulates water quality constituents associated with eutrophication in the lake, including phytoplankton, zooplankton, nitrogen, phosphorus, dissolved oxygen, and others. Various kinetic coefficients were calibrated using measured data or information from relevant literature, to study eutrophication in the lake. The values calculated by the calibrated model agree well with field data, including ammonia nitrogen, total nitrogen, total phosphorus and dissolved oxygen. Changes related to nutrition and dissolved oxygen during the processes were simulated. The present model describes the temporal variation of water quality in Baiyangdian Lake with reasonable accuracy. Deviations between model-simulated and observed values are discussed. As an ideal tool for environmental management of the lake, this model can be used to predict its water quality, and be used in research to examine the eutrophication process.展开更多
Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researche...Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researchers may find it costly to purchase commercial vectors from bio-companies or time-and labor-consuming to construct their own shRNA vectors using traditional method by inserting annealed duplex into digested vectors.Despite intensive efforts to accelerate shRNA vector cloning in laboratories,the development of a reliable,rapid,conven-ient,and cost-effective method is still in great demand.To this end,we developed a novel method named SuperSH(Super rapid cloning of shRNA vector)for the effective and rapid construction of shRNA-expressing vectors based on high-performance DNA polymerase and seamless cloning technique[1](Additional file 1:Fig-ure S1a;the detailed methods can be found in Additional file 1).In our SuperSH method,the shRNA sequences are introduced into the vector via a pair of polymerase chain reaction(PCR)primers rather than via annealed duplex.In detail,the 3′ends of the primers are designed to bind the template to initiate a PCR to amplify the vector back-bone,and the 5′portions are designed to introduce the sequences of interest as well as to form a short homol-ogous arm for subsequent recombination via seamless cloning[1].展开更多
基金supported by the National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82073267,82203399,82372689)+1 种基金Program for Outstanding Leading Talents in ShanghaiInnovative Research Team of High-level Local University in Shanghai。
文摘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.
基金Supported by China Agricultural Industry Research System(CARS-15-38).
文摘In recent years,the area dedicated to cotton cultivation in eastern Henan Province has experienced a continuous decline.Developing efficient multi-cropping systems for cotton and increasing the multiple cropping index represent effective strategies to stabilize the cotton planting area and enhance the income of cotton farmers.This paper presents an overview of intercropping systems and the benefits associated with cotton rotation and intercropping practices.Specifically,it discusses the"early maturing cotton-wheat"rotation system,the"cotton-watermelon"intercropping system,the"cotton-Dutch bean"intercropping system,and the"early maturing cotton-peanut-garlic"intercropping system.
基金supported by National Natural Science Foundation of China grants(Nos.81530075 and 81472741)the National Key Research and Development Program of China(Stem Cell and Translational Research 2016YFA0101202)the Ministry of Science and Technology(MOST) grant (No.2015CB553800)
文摘Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,and its protein BRCA1 plays a role in DNA repair[1].BRCA1 is generally expressed in the cells of mammary glands and other tissues,helping to repair damaged DNA or disrupting cells when DNA cannot be repaired.When BRCA1 is mutated and cannot function and therefore the damaged DNA cannot be repaired
基金supported by National Key Research and Development Program of China(2023YFC2506400,2020YFA0112300)National Natural Science Foundation of China(Grant Nos.82230103,81930075,82073267,82203399,82072903)+7 种基金“Ten Thousand Plan”—National High-Level Talents Special Support Plan WR-YK5202101Program of Shanghai Academic/Technology Research Leader 20XD1400700Program for Outstanding Medical Academic Leader in Shanghai(2019LJ04)The innovative research team of high-level local university in ShanghaiThe Fudan University Research Foundation(IDH 1340042)The Research Foundation of the Fudan University Shanghai Cancer Center(YJRC1603)Shanghai Anticancer Association EYAS PROJECT(SACA-CY23B07)The Natural Science Foundation of Hunan Province(2020JJ4916).
文摘Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression.However,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail.Here,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy.ETBF,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance.Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein.NOD1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs.NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.
基金The National Key Research and Development Program of China(2020YFA0112300)National Natural Science Foundation of China(82230103,81930075,82203399,82073267)+4 种基金“Ten Thousand Plan”-National High-Level Talents Special Support Plan(WR-YK5202101)Program for Outstanding Leading Talents in ShanghaiProgram for Outstanding Medical Academic Leader in Shanghai(2019LJ04)Program of Shanghai Academic/Technology Research Leader(20XD1400700)The innovative research team of high-level local university in Shanghai.
文摘Our previous studies have showed that C-C motif chemokine ligand 20(CCL20)advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell(BCSC)self-renewal.However,it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment(TME).Here,we observed that polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors.Mechanistically,CCL20 activated the differentiation of granulocyte-monocyte progenitors(GMPs)via its receptor C-C motif chemokine receptor 6(CCR6)leading to the PMN-MDSC expansion.PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors(CCL20-modulated PMN-MDSCs)secreted amounts of C-X-C motif chemokine ligand 2(CXCL2)and increased ALDH+BCSCs via activating CXCR2/NOTCH1/HEY1 signaling pathway.Furthermore,C-X-C motif chemokine receptor 2(CXCR2)antagonist SB225002 enhanced the docetaxel(DTX)effects on tumor growth by decreasing BCSCs in CCL20high-expressing tumors.These findings elucidated how CCL20 modulated the TME to promote cancer development,indicating a new therapeutic strategy by interfering with the interaction between PMN-MDSCs and BCSCs in breast cancer,especially in CCL20high-expressing breast cancer.
基金supported by the National Natural Science Foundation of China(Nos.82073688,82103971 and 81930075)Shanghai Science and Technology Development Fund from Central Leading Local Government(No.YDZX20223100001004,China)+1 种基金Science and Technology Commission of Shanghai Municipality(No.21S11907300,China)Program of Shanghai Academic/Technology Research Leader(No.20XD1400700,China)。
文摘Triple-negative breast cancer(TNBC)is a nasty disease with extremely high malignancy and poor prognosis.Annexin A3(ANXA3)is a potential prognosis biomarker,displaying an excellent correlation of ANXA3 overexpression with patients'poor prognosis.Silencing the expression of ANXA3effectively inhibits the proliferation and metastasis of TNBC,suggesting that ANXA3 can be a promising therapeutic target to treat TNBC.Herein,we report a first-in-class ANXA3-targeted small molecule(R)-SL18,which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells.(R)-SL18 directly bound to ANXA3 and increased its ubiquitination,thereby inducing ANXA3 degradation with moderate family selectivity.Importantly,(R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model.Furthermore,(R)-SL18 could reduce theβ-catenin level,and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells.Collectively,our data suggested that targeting degradation of ANXA3 by(R)-SL18 possesses the potential to treat TNBC.
文摘Cancer stem cells （CSCs）, a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA （ncRNA） including microRNAs and long non-coding RNAs （IncRNAs）, and histone-modifiers, such as let- 7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, IncRNAs and histone- modifiers especially Polycomb family proteins in regulating breast cancer stem cells （BCSCs）.
基金supported by the National Key R&D Program of China(2020YFA0803400/2020YFA0803402 and 2019YFA0801703 to Q.-Y.L.)the National Natural Science Foundation of China(81872240 to M.Y.,82002951 to J.L,and 81790250/81790253,91959202,and 82121004 to Q.-Y.L.)the Innovation Program of Shanghai Municipal Education Commission(N173606 to Q.-Y.L.).
文摘Folate metabolism plays an essential role in tumor development.Various cancers display therapeutic response to reagents targeting key enzymes of the folate cycle,but obtain chemoresistance later.Therefore,novel targets in folate metabolism are highly demanded.Methylenetetrahydrofolate dehydrogenase/methylenetetrahydrofolate cyclohydrolase 2(MTHFD2)is one of the key enzymes in folate metabolism and its expression is highly increased in mutiple human cancers.However,the underlying mechanism that regulates MTHFD2 expression remains unknown.Here,we elucidate that SIRT4 deacetylates the conserved lysine 50(K50)residue in MTHFD2.K50 deacetylation destabilizes MTHFD2 by elevating cullin 3 E3 ligase-mediated proteasomal degradation in response to stressful stimuli of folate deprivation,leading to suppression of nicotinamide adenine dinucleotide phosphate production in tumor cells and accumulation of intracellular reactive oxygen species,which in turn inhibits the growth of breast cancer cells.Collectively,our study reveals that SIRT4 senses folate availability to control MTHFD2 K50 acetylation and its protein stability,bridging nutrient/folate stress and cellular redox to act on cancer cell growth.
文摘Hydrodynamic, physical, and biochemical processes in the Baiyangdian Lake water environment were analyzed comprehensively. An eutrophication eco- dynamics model including the effects of reed resistance on flow was coupled with the hydrodynamics governing equations. An improvement on the Water Quality Analysis Simulation Program （WASP, a modeling system intro- duced by the US Environmental Protection Agency） is established, which uses the zooplankton kinetic equation. The model simulates water quality constituents associated with eutrophication in the lake, including phytoplankton, zooplankton, nitrogen, phosphorus, dissolved oxygen, and others. Various kinetic coefficients were calibrated using measured data or information from relevant literature, to study eutrophication in the lake. The values calculated by the calibrated model agree well with field data, including ammonia nitrogen, total nitrogen, total phosphorus and dissolved oxygen. Changes related to nutrition and dissolved oxygen during the processes were simulated. The present model describes the temporal variation of water quality in Baiyangdian Lake with reasonable accuracy. Deviations between model-simulated and observed values are discussed. As an ideal tool for environmental management of the lake, this model can be used to predict its water quality, and be used in research to examine the eutrophication process.
基金by the National Key Research and Development Program of China(Stem Cell and Translational Research 2016YFA0101202)National Nature Science Foundation of China Grants(81530075 and 81472741)+2 种基金Fudan University Research Foundation(IDH 1340042)Research Foundation of the Fudan University Shanghai Cancer Center(YJRC1603)the Ministry of Science and Technology of China Grant(2015CB553800).
文摘Dear Editor,Since the discovery of short hairpin RNA(shRNA)vec-tor-mediated RNA interference(RNAi),this technology has been widely used in cancer research for its specific-ity,potency,and convenience.However,researchers may find it costly to purchase commercial vectors from bio-companies or time-and labor-consuming to construct their own shRNA vectors using traditional method by inserting annealed duplex into digested vectors.Despite intensive efforts to accelerate shRNA vector cloning in laboratories,the development of a reliable,rapid,conven-ient,and cost-effective method is still in great demand.To this end,we developed a novel method named SuperSH(Super rapid cloning of shRNA vector)for the effective and rapid construction of shRNA-expressing vectors based on high-performance DNA polymerase and seamless cloning technique[1](Additional file 1:Fig-ure S1a;the detailed methods can be found in Additional file 1).In our SuperSH method,the shRNA sequences are introduced into the vector via a pair of polymerase chain reaction(PCR)primers rather than via annealed duplex.In detail,the 3′ends of the primers are designed to bind the template to initiate a PCR to amplify the vector back-bone,and the 5′portions are designed to introduce the sequences of interest as well as to form a short homol-ogous arm for subsequent recombination via seamless cloning[1].
