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Network biology approach to epithelial–mesenchymal transition in cancer metastasis: three stage theory

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Journal of Molecular Cell Biology 2015年第3期7卷 253-266页

作者： Hiroshi Tanaka Soichi Ogishima Department of Bioinformatics Medical Research InstituteTokyo Medical and Dental UniversityTokyoJapan Department of Bioclinical Informatics Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan

Epithelial–mesenchymal transition(EMT)plays a critical role in promoting cancer *** this study,cancer EMT is considered as an overall structural change in the gene regulatory network(GRN),and its essential features are elucidated by the network biology *** first defined the state space of GRN as a set of all possible activation patterns of GRN,and then introduced the quasipotential field into this space to show the relative stability distribution of each *** quasi-potential was determined empirically by collecting gene expression profiles from public *** of GRN states during the EMT process were traced in the state space,by using time-course data of gene expression profiles of a cell line inducingEMTfromthe *** wasfound that cancerEMT occurred in three sequential stable stages,each of which formed a potential basin along the EMT *** confirmation,structural changes of GRN were estimated by applying the ARACNe algorithm to the same time-course data,and then applying master regulator analysis to extract the main *** group of master regulators was found to be alternatively active in the subsequent three stages to cause overall structural changes of GRN during cancer EMT.

关键词： epithelial-mesenchymal transition(EMT) Waddington’s epigenetic landscape gene regulatory network GRN network stage space cancer metastasis

Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways

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Regenerative Biomaterials 2023年第1期10卷 574-589页

作者： Fengzhu Zhang Aiwen Zhang Youning Xie Haiying Wen Ranjith Kumar Kankala Jing Huang Anjun Zhang Qi Wang Biaoqi Chen Haiyan Dong Zhao Guo Aizheng Chen Dayun Yang Fujian Key Laboratory of Translational Research in cancer and Neurodegenerative Diseases School of Basic Medical SciencesFujian Medical UniversityFuzhou350108PR China Institute of Biomaterials and Tissue Engineering Huaqiao UniversityXiamen361021PR China Fujian Provincial Key Laboratory of Biochemical Technology(Huaqiao University) Xiamen361021PR China

cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer *** unique proline isomerase Pin1 activates numerous cancer pathways,but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are ***,the applicability of Pin1 inhibitor-all-trans retinoic acid(ATRA)is limited due to its several ***,uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles(ATRA-NPs)with high encapsulation efficiency,good cellular uptake,excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized ***-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular ***1 played a key role in cancer metastasis and was the main target of ***-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal *** ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth,it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

关键词： cancer metastasis targeted therapy Pin1 inhibitor nano delivery signaling pathway

A redox-responsive self-assembling COA-4-arm PEG prodrug nanosystem for dual drug delivery suppresses cancer metastasis and drug resistance by downregulating hsp90 expression

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Acta Pharmaceutica Sinica B 2023年第7期13卷 3153-3167页

作者： Yi Zhou Yingling Miao Qiudi Huang Wenwen Shi Jiacui Xie Jiachang Lin Pei Huang Chengfeng Yue Yuan Qin Xiyong Yu He Wang Linghao Qin Jianhai Chen Nanfang Hospital Southern Medical UniversityGuangzhou 510515China Key Laboratory of Molecular Target and Clinical Pharmacology and the State Key Laboratory of Respiratory Disease and the Fifth Affiliated Hospital School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China Center of cancer Research The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhou 510006China

metastasis and resistance are main causes to affect the outcome of the current anticancer *** shock protein 90(Hsp90)as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and *** Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and *** this study,a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX,and a COAmodified 4-arm PEG polymer(4PSC)was ***,an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression,was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory *** results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic *** blocking the Hsp90 signaling pathway,4PSC significantly enhanced the antitumor effect of PTX,inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in *** results were further confirmed in vivo with two preclinical tumor *** findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

关键词： 3-O-(Z)-Coumaroyloleanolic acid cancer metastasis Drug resistance Hsp90 Codelivery Prodrug nanosystem Chemotherapies Redox responsiveness

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2464-2482页

作者： Lingling Zhu Xianzhe Yu Ting Cao Hanyu Deng Xiaojun Tang Qing Lin Qinghua Zhou Lung cancer Center/Lung cancer Institute West China Hospital&West China School of PharmacyKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan UniversityChengdu 610065China Department of Gastrointestinal Surgery Chengdu Second People's HospitalChengdu 610065China Laboratory of Infectious Diseases and Vaccine West China HospitalSichuan UniversityChengdu 610065China

metastasis is the leading cause of cancer-related *** extensive treatment,the prognosis for patients with metastatic cancer remains *** addition to conventional surgical resection,radiotherapy,immunotherapy,chemotherapy,and targeted therapy,various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target ***,nanomedicines exhibit certain limitations in clinical applications,such as rapid clearance from the body,low biological stability,and poor targeting *** methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these *** the involvement of immune cells in the tumor microenvironment of the metastatic cascade,biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high *** this review,we explore the impact of immune cells on various processes of tumor ***,we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion,prolonged circulation,enhanced tumor accumulation,and immunosuppression of the tumor ***,we describe the prospects and existing challenges in clinical translation.

关键词： Biomimetic nanoparticles cancer metastasis Tumor microenvironment Immune system Immune cell membrane Tumor-homing Biocompatibility

Developmental pathways associated with cancer metastasis:Notch,Wnt,and Hedgehog

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cancer Biology & Medicine 2017年第2期14卷 109-120页

作者： Armel Herve Nwabo Kamdje Paul Takam Kamga Richard Tagne Simo Lorella Vecchio Paul Faustin Seke Etet Jean Marc Muller Giulio Bassi Erique Lukong Raghuveera Kumar Goel Jeremie Mbo Amvene Mauro Krampera Department of Biomedical Sciences University of Ngaoundere Laboratory University of Verona Department of Basic Health SciencesCollege of Applied Medical SciencesQassim University Faculty of Science University of Poitiers Department of Biochemistry College of MedicineUniversity of Saskatchewan

Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death,motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers. metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed.

关键词： cancer metastasis developmental pathways Notch Wnt Hedgehog therapeutic targets

MAGE-C3 promotes cancer metastasis by inducing epithelial-mesenchymal transition and immunosuppression in esophageal squamous cell carcinoma

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cancer Communications 2021年第12期41卷 1354-1372页

作者： Qingnan Wu Weimin Zhang Yan Wang Qingjie Min Hongyue Zhang Dezuo Dong Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142P.R.China Shenzhen Bay Laboratory Institute of Cancer ResearchShenzhenGuangdong 518107P.R.China Research Unit of Molecular cancer Research Chinese Academy of Medical SciencesBeijing 100142P.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Radiation OncologyPeking University Cancer Hospital&InstituteBeijing 100142P.R.China

Background:Evading immune surveillance is necessary for tumor ***,there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune *** this study,we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma(ESCC).Methods:The expression of melanoma-associated antigen C3(MAGE-C3)was detected using *** assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma(ESCC)*** assays in mice were used to evaluate metastatic ability in ***-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor *** sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control *** ontology(GO)enrichment analyses was performed to identify the most altered pathways influenced by *** activation of the interferon-γ(IFN-γ)pathway was analyzed using Western blotting,GAS luciferase reporter assays,immunofluorescence,and flow *** role of MAGE-C3 in the IFN-γpathway was determined by Western blotting and ***,immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung ***:MAGE-C3 was overexpressed in ESCC *** expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with *** experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition(EMT).MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells,implying an immunosuppressive ***,MAGE-C3 facilitated IFN-γsignaling and upregulated programmed cell death ligand 1(PDŋL1)by binding with IFN-γreceptor 1(IFNGR1)and st

关键词： cancer metastasis epithelial-mesenchymal transition esophageal squamous cell carcinoma immunosuppression interferon-γreceptor interferon-γ melanoma-associated antigen C3

Exosomal long non-coding RNAs:Emerging players in cancer metastasis and potential diagnostic biomarkers for personalized oncology

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Genes & Diseases 2021年第6期8卷 769-780页

作者： Hui Nie Zhujun Liao Yutong Wang Jianhua Zhou Xiaoyun He Chunlin Ou Department of Pathology Xiangya HospitalCentral South UniversityChangshaHunan Province410008PR China Department of Rheumatology and Immunology Xiangya HospitalCentral South UniversityChangshaHunan Province410008PR China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan Province410008PR China

metastasis is a major challenge in the treatment of *** are a class of small extracellular vesicles(EVs)that play critical roles in several human diseases,especially cancer,by transferring information(e.g.,DNA,RNA,and protein)via cell-to-cell *** recent studies have shown that exosomal long non-coding RNAs(lncRNAs)play crucial regulatory roles in cancer metastasis in the tumor microenvironment by altering the expression of several key signaling pathways and *** to their specificity and sensitivity,exosomal lncRNAs have potential as novel tumor markers and therapeutic targets in the treatment of cancer *** this review,we aim to summarize the roles of exosomal lncRNAs in cancer metastasis,the mechanisms underlying their roles,and their potential clinical applications.

关键词： cancer metastasis Exosomes Extracellular vesicles Long noncoding RNA Therapy Tumor marker

Emerging Regulatory Mechanisms of N6-Methyladenosine Modification in cancer metastasis

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Phenomics 2023年第1期3卷 83-100页

作者： Jing Zhao Hao Xu Yinghan Su Junjie Pan Sunzhe Xie Jianfeng Xu Lunxiu Qin Department of General Surgery Huashan HospitalFudan University12 Urumqi Road(M)Shanghai 200040China cancer metastasis Institute Fudan UniversityShanghai 200120China

cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and *** evidence demonstrates that m^(6)A plays a critical role in regulating cancer ***,there is a lack of studies that review the recent advances of m^(6)A in cancer ***,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various ***,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer *** review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.

关键词： cancer metastasis m^(6)A Epitranscriptomic modification RNA metabolism Organ-specific metastasis

Two-Stage Segmentation of Lung cancer metastasis Lesions by Fusion of Multi-Resolution Features

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Health 2023年第5期15卷 436-456页

作者： Jingwen Zhao Xinyu Wang Yunlang She Shuohong Wang School of Electronic and Electric Engineering Shanghai University of Engineering Science Shanghai China Shanghai Pulmonary Hospital Shanghai China Department of Molecular and Cellular Biology and Center for Brain Science Harvard University Cambridge MA USA

The deep learning method automatically extracts advanced features from a large amount of data, avoiding cumbersome manual feature screening, and using digital pathology and artificial intelligence technology to build a computer-aided diagnosis system to help pathologists quickly make objective and reliable diagnoses and improve work efficiency. Because pathological images are limited by factors such as sample size, manual labeling expertise, and complexity, artificial intelligence algorithms have not been extensively and in-depth researched on pathological images of lung cancer metastasis. Therefore, this paper proposes a lung cancer metastasis segmentation method based on pathological images, to further improve the computer-aided diagnosis method of lung cancer.

关键词： Transfer Learning Pathological Image ACR-UNet Deep Learning cancer metastasis