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MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme

Cancer Biology & Medicine 2020年第1期17卷 101-111页

作者： Sharan Malagobadan Chai San Ho Noor Hasima Nagoor Institute of Biological Sciences(Genetics&Molecular Biology) Faculty of ScienceUniversity of MalayaKuala Lumpur 50603Malaysia Center for Research in Biotechnology for Agriculture(CEBAR) University of MalayaKuala Lumpur 50603Malaysia

Objective:anoikis is apoptosis that is induced when cells detach from the extracellular matrix and neighboring *** anoikis serves as a regulatory barrier,cancer cells often acquire resistance towards anoikis during tumorigenesis to become ***(miRNAs)are short strand RNA molecules that regulate genes post-transcriptionally by binding to mRNAs and reducing the expression of its target *** study aimed to elucidate the role of a novel miRNA,miR-6744-5 p,in regulating anoikis in breast cancer and identify its target ***:An anoikis resistant variant of the luminal A type breast cancer MCF-7 cell line(MCF-7-AR)was generated by selecting and amplifying surviving cells after repeated exposure to growth in *** RNA microarray analysis identified a list of dysregulated miRNAs from which miR-6744-5 p was chosen for overexpression and knockdown studies in ***,the miRNA was also overexpressed in a triple-negative breast cancer cell line,MDA-MB-231,to evaluate its ability to impair the metastatic potential of breast cancer ***:This study showed that overexpression and knockdown of miR-6744-5 p in MCF-7 increased and decreased anoikis sensitivity,***,overexpression of miR-6744-5 p in MDA-MB-231 increased anoikis and also decreased tumor cell invasion in vitro and in ***,NAT1 enzyme was identified and validated as the direct target of miR-6744-5 ***:This study has proven the ability of miR-6744-5 p to increase anoikis sensitivity in both luminal A and triple negative breast cancer cell lines,highlighting its therapeutic potential in treating breast cancer.

关键词： anoikis miRNA breast cancer metastasis NAT1

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Advancements in precision nanomedicine design targeting the anoikis-platelet interface of circulating tumor cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3457-3475页

作者： Manqing Tang Zhijie Zhang Ping Wang Feng Zhao Lin Miao Yuming Wang Yingpeng Li Yunfei Li Zhonggao Gao College of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Component-Based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Tumor metastasis,the apex of cancer progression,poses a formidable challenge in therapeutic *** tumor cells(CTCs),resilient entities originating from primary tumors or their metastases,significantly contribute to this process by demonstrating remarkable *** survive shear stress,resist anoikis,evade immune surveillance,and thwart *** comprehensive review aims to elucidate the intricate landscape of CTC formation,metastatic mechanisms,and the myriad factors influencing their *** signaling pathways,such as integrin-related signaling,cellular autophagy,epithelial-mesenchymal transition,and interactions with platelets,are examined in ***,we explore the realm of precision nanomedicine design,with a specific emphasis on the anoikis‒platelet *** innovative approach strategically targets CTC survival mechanisms,offering promising avenues for combatting metastatic cancer with unprecedented precision and *** review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

关键词： CTCs anoikis Platelet Cancer stem cell Metastasis Platelet‒CTC interaction Platelet targeting Nanomedicines

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Apigenin is an anoikis sensitizer with strong anti-metastatic properties in experimental breast cancer

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Food Science and Human Wellness 2024年第4期13卷 2221-2233页

作者： Ruijie Xu Zhijie Yao Hao Zhang Haitao Li Wei Chen State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China

Loss of susceptibility to anoikis signals is a crucial step in *** resistance therefore represents a promising adjuvant therapeutic target for cancer *** this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily *** 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of ***,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in ***,we demonstrated that the thromboxane A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling *** of TXA_(2)signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer ***_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)biosynthesis in vitro and in ***,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.

关键词： Apigenin anoikis Breast cancer metastasis Thromboxane A2

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Comprehensive bioinformatics analysis and experimental validation:An anoikis-related gene prognostic model for targeted drug development in head and neck squamous cell carcinoma

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Oncology Research 2023年第5期31卷 715-752页

作者： LIN QIU ANQI TAO XIAOQIAN SUN FEI LIU XIANPENG GE CUIYING LI Central Laboratory Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing100081China Department of Dentistry Xuanwu Hospital Capital Medical UniversityBeijing100053China National Clinical Research Center for Geriatric Disorders Beijing100101China School of Medicine Nankai UniversityTianjin300071China Department of Oral and Maxillofacial Surgery Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin300041China

We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted *** expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was *** results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus *** correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic *** small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD ***,in vitro experiments were used to verify the database *** relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model ***5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 *** docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in ***,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.

关键词： Head and neck squamous cell carcinoma anoikis Prognosis Proliferation Apoptosis

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EZH2 Contributes to anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A

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Current Medical Science 2023年第4期43卷 794-802页

作者： Shao-hai WANG Lin LIU Ke-yong BAO Yi-fan ZHANG Wen-wen WANG Shi DU Na-er JIA Suo SUO Jing CAI Jian-feng GUO Gang LV Department of Obstetrics and Gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Obstetrics and Gynecology Affiliated Hospital of Inner Mongolia University for The NationalitiesTongliao 028000China Department of Obstetrics and Gynecology Bozhou Branch of Union HospitalBozhou 833400China Department of Obstetrics and Gynecology Bozhou People's HospitalBozhou 833400China

Objective:Histone modification has a significant effect on gene *** of zeste homolog 2(EZH2)contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase *** development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant *** purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal ***:In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues,we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude *** resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine(m6A)levels were ***:EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian *** the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo.M6a regulation altered the effect of EZH2 on anoikis ***:Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A *** findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

关键词： anoikis heterografts N6-methyladenosine enhancer of zeste homolog 2 ovarian neoplasms

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Mammalian Ste20-like kinase 1 inhibition as a cellular mediator of anoikis in mouse bone marrow mesenchymal stem cells

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World Journal of Stem Cells 2023年第3期15卷 90-104页

作者： Tao Zhang Qian Zhang Wan-Cheng Yu Department of Cardiovascular Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250062Shandong ProvinceChina

BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of *** a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase the production of reactive oxygen species(ROS),thereby promoting ***,we found that Mst1 inhibition could protect mouse bone marrow MSCs(mBMSCs)from H 2 O 2-induced cell apoptosis by inducing autophagy and reducing ROS ***,the influence of Mst1 inhibition on anoikis in mBMSCs remains *** To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated *** Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA(shRNA)adenovirus ***(ITGs)were tested by flow *** and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA,*** alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis *** levels of the anoikis-related proteins ITGα5,ITGβ1,and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I,Beclin1 and p62 were detected by Western *** In isolated mBMSCs,Mst1 expression was upregulated,and Mst1 inhibition significantly reduced cell apoptosis,induced autophagy and decreased ROS ***,we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4,ITGαv,or ITGβ3 ***,autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting *** Mst1 inhibition ameliorated autophagy formation,increased ITGα5β1 expression,and decreased the excessive production of ROS,thereby reducing cell apoptosis in isolated *** on these results,Mst

关键词： Mouse bone marrow mesenchymal stem cell Mammalian sterile 20-like kinase 1 anoikis Integrin Autophagy Reactive oxygen species

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Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma

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中南大学学报（医学版） 2024年第5期49卷 758-774页

作者： WANG Dong DENG Qing PENG Yi TONG Zhaochen LI Zixin HUANG Liping ZENG Jin LI Jinsong MIAO Jinglei CHEN Shijie Department of Spine Surgery Third Xiangya HospitalCentral South UniversityChangsha 410013 Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor ***-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary ***,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune *** study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of ***:anoikis-related genes(ANRGs)were obtained from *** information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)*** highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)*** learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO ***,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor ***:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic *** differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling ***:The prognostic model based on ANRGs and tumor microenvironment

关键词： anoikis tumor immune microenvironment bioinformatics prognosis osteosarcoma

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Cellular Anchorage Sensing and anoikis

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Clinical oncology and cancer researeh 2011年第1期8卷 16-20页

作者： Wei DU Zhi-chao ZHENG Zhe LIU Zhen-yi MA Research Center of Basic Medical Sciences Basci Medical College Tianjin Medical University Tianjin 300070 China

Normal epithelial cells that lose the integrindependent anchorage to their extracellular matrix trigger anoikis,while metastatic tumor cells bypass anoikis pathway, which is one of the key events to achieve the metastasis. Physiological role of anoikis is also involved during embryonic development and tissue homeostasis, suggesting that anoikis must be strictly regulated at some level. Despite its importance, the molecular pathways involved in the regulation of anoikis and the proximal signals reporting loss of anchorage are poorly understood. Recent studies suggest an adaptor protein p66Shc, localizing at focal adhesions,mediates anoikis through activation of RhoA. However, expression of p66Shc is inadequate in metastatic cancer cells, failing to initiate anoikis and promoting tumor metastasis. Reexpression of proapoptotic protein p66Shc can restore the susceptibility to ***, p66Shc may be a potential target molecule for diagnosis of tumor metastasis and for tumor treatment.

关键词： p66Shc metastasis anoikis adaptor protein signal transduction

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anoikis induction by glycoprotein from <i>Laminaria japonica</i>in HT-29 cells

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Open Journal of Preventive Medicine 2011年第2期1卷 49-61页

作者： Hiroe Go Hye-Jung Hwang In-Hye Kim Taek-Jeong Nam Department of Food Science and Nutrition Pukyong National University 599-1 Daeyeon 3-dong Nam-gu Busan 608-737 The Re-public of KOREA

We extracted a glycoprotein from the brown alga Laminaria japonica (LJGP). We previously demonstrated that LJGP induced apop- tosis in HT-29 colon cancer cells via the Fas- and the mitochondrial signaling pathway, and cell-cycle arrest. However, its effect on the cell membrane remained unknown. In this study, we identified the involvement of matrix metalloproteinase (MMP), integrin, and Epi- thelial (E)-cadherin in LJGP-induced apoptosis in HT-29 cells. LJGP treatment increased the expression and activity of MMP-2 and MMP-9. Furthermore, LJGP decreased the expression of integrin αν, β3, β5, β6 and E- cadherin. Consistent with a decreased expression of E-cadherin, LJGP inhibited the Wnt signaling pathway. Moreover, activation of downstream molecules of integrin, including focal adhesion kinase (FAK), the Src family of protooncogenic tyrosine kinases, extracellular signal-related kinase (ERK), and phosphatidyl inositol 3 kinase (PI-3K) were also decreased. These findings suggest that LJGP-induced apoptosis of HT-29 cells involves possible ECM disruption and cell detachment, which are executed principally through the activation of MMPs and by a decrease of adhesion molecules, contributing to a down-regulation of the PI-3K, MAPK, and Wnt signaling pathways. Apoptosis induced by ECM disruption or cell detachment is also known as anoikis. We can say that LJGP induces anoikis in HT-29 cells.

关键词： anoikis Glycoprotein Integrin Laminaria Japonica MMP Seaweed

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Inhibition of signal transducer and activator of transcription 3 expression by RNA interference suppresses invasion through inducing anoikis in human colon cancer cells

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World Journal of Gastroenterology 2008年第3期14卷 428-434页

作者： Yu Fan You-Li Zhang Ying Wu Wei Zhang Yin-Huan Wang Zhao-Ming Cheng Hua Li Department of Gastroenterology Affiliated Hospital Jiangsu University Zhenjiang 212001 Jiangsu ProvinceChina Department of Pharmacology and Toxicology DartmouthMedical School Dartmouth Medical School Har~over NH 03755United States

AIM:To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference. METHODS: Small interfering RNA (siRNA) targeting Signal transducer and activator of transcription 3 (STAT3) was transfected into HT29 colon cancer cells. STAT3 protein level and DNA-binding activity of STAT3 was evaluated by western blotting and electrophoretic mobility shift assay (EMSA), respectively. We studied the anchorage-independent growth using colony formation in soft agar, and invasion using the boyden chamber model, anoikis using DNA fragmentation assay and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), respectively. Western blot assay was used to observe the protein expression of Bcl-xL and survivin in colon cancer HT29 cells. RESULTS: RNA interference (RNAi) mediated by siRNA leads to suppression of STAT3 expression in colon cancer cell lines. Suppression of STAT3 expression by siRNA could inhibit anchorage-independent growth, and invasion ability, and induces anoikis in the colon cancer cell line HT29. It has been shown that knockdown of STAT3 expression by siRNA results in a reduction in expression of Bcl-xL and survivin in HT29 cells. CONCLUSION: These results suggest that STAT3 siRNA can inhibit the invasion ability of colon cancer cells through inducing anoikis, which antiapoptotic genes survivin and Bcl-xL contribute to regulation of *** studies indicate STAT3 siRNA could be a useful therapeutic tool for the treatment of colon cancer.

关键词： Colon cancer Invasion Signal transducerand activator of transcription 3 anoikis

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