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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang ceshi chen Affiliated Hospital of Guangdong Medical University Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research Center of Guizhou Medical University GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Center KunmingYunnan 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

EphA2:A promising therapeutic target in breast cancer

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Journal of Genetics and Genomics 2021年第4期48卷 261-267页

作者： Ping Zhao Dewei Jiang Yunchao Huang ceshi chen Department of the First Breast Surgery The Third Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Department of Thoracic Surgery The Third Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650118China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Affiliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou 510095China

Ephrin type-A receptor 2(EphA2),a receptor tyrosine kinase,is overexpressed in human breast cancers often linked to poor patient prognosis.Accumulating evidence demonstrates that EphA2 plays important roles in several critical processes associated with malignant breast progression,such as proliferation,survival,migration,invasion,drug resistance,metastasis,and angiogenesis.As its inhibition through multiple approaches can inhibit the growth of breast cancer and restore drug sensitivity,EphA2 has become a promising therapeutic target for breast cancer treatment.Here,we summarize the expression,functions,mechanisms of action,and regulation of EphA2 in breast cancer.We also list the potential therapeutic strategies targeting EphA2.Furthermore,we discuss the future directions of studying EphA2 in breast cancer.

关键词： EphA2 EphrinA1 Breast cancer Targeted therapy ADC

Characterization of tree shrew telomeres and telomerase

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Journal of Genetics and Genomics 2021年第7期48卷 631-639页

作者： Jian Sun Wenjing Liu Yongbo Guo Hailin Zhang Dewei Jiang Ying Luo Rong Liu ceshi chen Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province National Resource Center for Non-Human PrimatesKunming Primate Research CenterNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyKunmingYunnan 650201China Kunming College of Life Sciences University of Chinese Academy SciencesKunmingYunnan 650204China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Laboratory of Molecular Genetics of Aging&Tumor Medical FacultyKunming University of Science and TechnologyKunmingYunnan 650500China

The use of tree shrews as experimental animals for biomedical research is a new practice.Several recent studies suggest that tree shrews are suitable for studying cancers,including breast cancer,glioblastoma,lung cancer,and hepatocellular carcinoma.However,the telomeres and the telomerase of tree shrews have not been studied to date.Here,we characterize telomeres and telomerase in tree shrews.The telomere length of tree shrews is approximately 23 kb,which is longer than that of primates and shorter than that of mice,and it is extended in breast tumor tissues according to Southern blot and flow-fluorescence in situ hybridization(FISH)analyses.Tree shrew spleen,bone marrow,testis,ovary,and uterus show high telomerase activities,which are increased in breast tumor tissues by telomeric repeat amplification protocol assays.The telomere length becomes shorter,and telomerase activity decreases with age.The tree shrew TERT and TERC are more highly similar to primates than to rodents.These findings lay a solid foundation for using tree shrews to study aging and cancers.

关键词： Tree shrews Telomere TERT TERC Breast cancer

WWOX suppresses KLF5 expression and breast cancer cell growth

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Chinese Journal of Cancer Research 2014年第5期26卷 511-516页

作者： Fei Ge Wenlin chen Runxiang Yang Zhongmei Zhou Nanshan Chang ceshi chen Tianning Zou Rong Liu Jing Tan Guosheng Ren Department of Endocrine Surgery The First Affiliated Hospital of Chongqing Medical University Department of Breast Surgery The 3rd Affiliated Hospital of Kunming Medical University Second Department of Internal Medicine of Oncology The 3rd Affiliated Hospital of Kunming Medical University Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Institute of Molecular Medicine National Cheng Kung University Medical College

The WW domain-containing oxidoreductase（WWOX） is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX＇s role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5—an oncogenic transcription factor—at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former＇s WW domains and the latter＇s PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.

关键词： WW domain-containing oxidoreductase （VV-WOX） KLF5 breast cancer

Targeting HECTD3-IKKα axis inhibits inflammation-related metastasis

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3494-3511页

作者： Fubing Li Huichun Liang Hua You Ji Xiao Houjun Xia Xi chen Maobo Huang Zhuo cheng Chuanyu Yang Wenjing Liu Hailin Zhang Li Zeng Yingying Wu Fei Ge Zhen Li Wenhui Zhou Yi Wen Zhongmei Zhou Rong Liu Dewei Jiang Ni Xie Bin Liang Zhenzhen Liu Yanjie Kong ceshi chen Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Affliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou 510095China Department of Pathology School of Basic MedicineYunnan University of Chinese MedicineKunming 650500China Cllege of Life Science and Technology Guangzhou Jinan Biomedicine Research and Development CenterJinan UniversityGuangzhou 510632China Center for Cancer Immunology Institute of Biomedicine and BiotechnologyShenzhen Instituteof Advanced TechnologyChinese Academy of SciencesShenzhen 518055China First Affliated Hospital of Kunming Medical University KunmingYunnan 650032China Department of the Third Breast Surgery the Third Affliated Hospital of Kunming Medical UniversityKunmingYunnan 650118China Hubei Key Laboratory of Embryonic Stem Cell Research Hubei University of MedicineShiyan 442000China Biobank Shenzhen Second People's Hospitalthe First Affliated Hospital of Shenzhen UniversityHealth Science CenterShenzhen 518035China Center for Life Sciences School of Life SciencesYunnan UniversityKunmingYunnan 650091China Department of Breast disease Henan Breast Cancer CenterAffliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou450008China

Metastasis is the leading cause of cancer-related death.The interactions between circulating tumor cells and endothelial adhesion molecules in distant organs is a key step during extravasation in hematogenous metastasis.Surgery is a common intervention for most primary solid tumors.However,surgical trauma-related systemic inflammation facilitates distant tumor metastasis by increasing the spread and adhesion of tumor cells to vascular endothelial cells(ECs).Currently,there are no effective interventions to prevent distant metastasis.Here,we show that HECTD3 deficiency in ECs significantly reduces tumor metastasis in multiple mouse models.HECTD3 depletion downregulates expression of adhesion molecules,such as VCAM-1,ICAM-1 and E-selectin,in mouse primary ECs and HUVECs stimulated by inflammatory factors and inhibits adhesion of tumor cells to ECs both in vitro and in vivo.We demonstrate that HECTD3 promotes stabilization,nuclear localization and kinase activity of IKKa by ubiquitinating IKKa with K27-and K63-linked polyubiquitin chains at K296,increasing phosphorylation of histone H3 to promote NF-kB target gene transcription.Knockout of HECTD3 in endothelium significantly inhibits tumor cells lung colonization,while conditional knockin promotes that.IKKa kinase inhibitors prevented LPS-induced pulmonary metastasis.These findings reveal the promotional role of the HECTD3-IKKa axis in tumor hematogenous metastasis and providea potential strategy for tumormetastasis prevention.

关键词： metastasis Surgery organs

Glucose-6-phosphate dehydrogenase neutralizes stresses by supporting reductive glutamine metabolism and AMPK activation

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Signal Transduction and Targeted Therapy 2021年第3期6卷 580-583页

作者： Benfu Zhong Dewei Jiang Yang Hong Lifang Li Li Qiu Ronghui Yang Xiaohan Jin Yawen Song ceshi chen Binghui Li Department of Cancer Cell Biology and National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and HospitalTianjin 300060P.R.China Department of Biochemistry and Molecular Biology Capital Medical UniversityBeijing 100069P.R.China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China

Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we reveal a previously unidentified function of G6PD.It,even the natural G6PD deficiency-associated mutant without the activity to maintain the normal oxPPP,can antagonize the stresses by supporting the reductive glutamine metabolism and AMPK activation,independently of the NADPH generation by the oxPPP.

关键词： supporting reductive oxidative

A functional missense variant in ITIH3 affects protein expression and neurodevelopment and confers schizophrenia risk in the Han Chinese population

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Journal of Genetics and Genomics 2020年第5期47卷 233-248页

作者： Kaiqin Li Yifan Li Junyang Wang Yongxia Huo Di Huang Shiwu Li Jiewei Liu Xiaoyan Li Rong Liu Xiaogang chen Yong-Gang Yao ceshi chen Xiao Xiao Ming Li Xiong-Jian Luo Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming650223China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming650223China Institute of Mental Health National Clinical Research Center for Mental Health Disorders and National Technology Institute of PsychiatryThe Second Xiangya HospitalCentral South UniversityChangsha410011China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunming650223China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai200031China

The Psychiatric Genomics Consortium(PGC)has recently identified 10 potential functional coding variants for schizophrenia.However,how these coding variants confer schizophrenia risk remains largely unknown.Here,we investigate the associations between eight potential functional coding variants identified by PGC and schizophrenia in a large Han Chinese sample(n=4022 cases and 9270 controls).Among the eight tested single nucelotide polymorphisms(SNPs),rs3617(a missense variant,p.K315 Q in the ITIH3 gene)showed genome-wide significant association with schizophrenia in the Han Chinese population(P=8.36×10-16),with the same risk allele as in PGC.Interestingly,rs3617 is located in a genomic region that is highly evolutionarily conserved,and its schizophrenia risk allele(C allele)was associated with lower ITIH3 mRNA and protein expression.Intriguingly,mouse neural stem cells stably overexpressing ITIH3 with different alleles of rs3617 exhibited significant differences in proliferation,migration,and differentiation,suggesting the impact of rs3617 on neurodevelopment.Subsequent transcriptome analysis found that the differentially expressed genes in neural stem cells stably overexpressing different alleles of rs3617 were significantly enriched in schizophrenia-related pathways,including cell adhesion,synapse assembly,MAPK and PI3 K-AKT pathways.Our study provides convergent lines of evidence suggesting that rs3617 in ITIH3 likely affects protein function and neurodevelopment and thereby confers risk of schizophrenia.

关键词： Schizophrenia ITIH3 Missense variant Association Neurodevelopment Neural stem cells

Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORCl and scavenging ROS

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1907-1919页

作者： Jiao Wu Sai-Ching Jim Yeung Sicheng Liu Aiham Qdaisat Dewei Jiang Wenli Liu Zhuo cheng Wenjing Liu Haixia Wang Lu Li Zhongmei Zhou Rong Liu Chuanyu Yang ceshi chen Runxiang Yang Department of the Second Medical Oncology The Third Affiliated Hospital of Kunming Medical UniversityKunmingYunnan ProvinceChina Department of Emergency Medicine The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina Department of Palliative Rehabilitation and Integrative MedicineThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdongChina KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina Institute of Translation Medicine Shenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhenChina

Weight loss and cachexia are common problems in colorectal cancer patients;thus,parenteral and enteral nutrition support play important roles in cancer care.However,the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied.In this study,we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival(P<0.001)than those who did not.Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice,predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis,resulting in mTORCl activation.mTORCl inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation.In addition,cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione.We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin.These findings indicate that cyst(e)ine;as part of supplemental nutrition,plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

关键词： colon chemotherapy formulation

CACA Guidelines for Holistic Integrative Management of Breast Cancer

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Holistic Integrative Oncology 2022年第1期1卷 76-126页

作者： Jiong Wu Daiming Fan Zhimin Shao Binghe Xu Guosheng Ren Zefei Jiang Yongsheng Wang Feng Jin Jin Zhang Qingyuan Zhang Fei Ma Jinli Ma Zhonghua Wang Shusen Wang Xiaojia Wang Shu Wang Haibo Wang Tao Wang Xiang Wang Jing Wang Jia Wang Biyun Wang Li Fu Hongyuan Li Yehui Shi Lu Gan Yunjiang Liu Jian Liu Zhenzhen Liu Qiang Liu Qiang Sun Wenwu cheng Keda Yu Zhongsheng Tong Xinhong Wu Chuangui Song Jianguo Zhang Jian Zhang Junjie Li Bin Li Man Li Huiping Li Wentao Yang Hongjian Yang Benlong Yang Hong Bu Juping Shen Zhenzhou Shen Yiding chen ceshi chen Da Pang Zhimin Fan Ying Zheng Xiaoli Yu Guangyu Liu Xichun Hu Yiqun Ling Jinhai Tang Yongmei Yin Cuizhi Geng Peng Yuan Yajia Gu Cai Chang Xuchen Cao Yuan Sheng Yuanxi Huang Jian Huang Weijun Peng Xiaohua Zeng Yuntao Xie Ning Liao Committee of Breast Cancer Society,Chinese Anti-Cancer Association Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai Medical College of Fudan UniversityShanghaiChina Department of Oncology Shanghai Medical College of Fudan UniversityShanghaiChina Department of Gastroenterology Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina State key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anChina National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Endocrine and Breast Surgery The First Affliated Hospital of Chongqing Medical UniversityYuzhongChongqingChina Medicine-Oncology The Affliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese People’s Liberation Army)BeijingChina Breast Disease Center Shandong Cancer HospitalJinanChina Department of Breast Surgery The First Affliated Hospital of China Medical UniversityShenyangChina The 3rd Department of Breast Cancer China Tianjin Breast Cancer PreventionTreatment and Research CenterTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center of CancerTianjinChina Harbin Medical University Cancer Hospital HarbinChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghai Medical College of Fudan UniversityShanghaiChina Sun Yat-Sen University Cancer Center GuangzhouChina Zhejiang Cancer Hospital HangzhouChina Breast Center Peking University People’s HospitalBeijingChina Department of Breast Center The Affliated Hospital of Qingdao UniversityShandongChina Department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Departmen

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

关键词： Epidemiology of breast cancer Breast cancer screening Breast cancer diagnosis Early breast cancer treatment Advanced breast cancer treatment Traditional Chinese medicine treatment of breast cancer

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上皮间质转化与乳腺癌干细胞的关系

贵州医科大学学报 2022年第11期47卷 1241-1263,1273页

作者：吴婷月陈雯敏陈策实中国科学技术大学生命科学与医学部安徽合肥230026 中国科学院昆明动物研究所云南省动物模型与人类疾病机理重点实验室云南昆明650221 中国科学院大学存济医学院北京100049 昆明医科大学生物医学工程研究院云南昆明650504 云南省肿瘤医院云南昆明650118

上皮间质转化(EMT)通过改变乳腺癌细胞的基因表达谱,调控与干性、迁移及耐药相关基因的表达,促进乳腺癌细胞的发生、转移、耐药及复发。肿瘤微环境因子通过细胞内的转录因子、表观因子、信号通路同时调节EMT和干性。本述评聚焦阐述了EM... 详细信息

上皮间质转化(EMT)通过改变乳腺癌细胞的基因表达谱,调控与干性、迁移及耐药相关基因的表达,促进乳腺癌细胞的发生、转移、耐药及复发。肿瘤微环境因子通过细胞内的转录因子、表观因子、信号通路同时调节EMT和干性。本述评聚焦阐述了EMT与乳腺癌干细胞之间的关系,探讨乳腺癌的潜在治疗策略。

关键词：上皮间质转化乳腺癌干细胞肿瘤异质性肿瘤微环境信号通路靶向治疗