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Fine-tuning cell organelle dynamics during mitosis by small GTPases

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Frontiers of Medicine 2022年第3期16卷 339-357页

作者： Zijian Zhang Wei Zhang quentin liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Clinical Immunology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Institute of Cancer Stem Cell Dalian Medical UniversityDalian 116044China

During mitosis,the allocation of genetic material concurs with organelle transformation and *** coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression,cell fate determination,and organismal *** GTPases belonging to the Ras superfamily regulate various cell organelles during *** the key regulators of membrane dynamics,the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases,such as cancer and Alzheimer’s *** discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure *** review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

关键词： small GTPase cell organelle mitosis

New insights from the widening homogeneity perspective to target intratumor heterogeneity

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Cancer Communications 2018年第1期38卷 195-201页

作者： Mengying Tong Ziqian Deng Xiaolong Zhang Bin He Mengying Yang Wei Cheng quentin liu Institute of Cancer Stem Cell Cancer CenterDalian Medical UniversityDalian 116044LiaoningP.R.China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhou 510630GuangdongP.R.China Department of Hematology The Third Affiliated HospitalSun Yat-sen UniverisityGuangzhou 510630GuangdongP.R.China

Precision medicine has shed new light on the treatment of heterogeneous cancer ***,intratumor heterogeneity strongly constrains the clinical benefit of precision ***,rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions,but also provide an avenue for precision ***,we explore the current approaches for targeting intratumor hetero-geneity and their ***,we propose a theoretical strategy with a“homogenization”feature based on iatrogenic evolutionary selection to target intratumor heterogeneity.

关键词： Acquired drug resistance Homogenization Intratumor heterogeneity Plasticity Precision medicine

STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5106-5118页

作者： Ze-Wei Huang Xue-Ning Zhang Ling Zhang Ling-Ling liu Jing-Wen Zhang Yu-Xiang Sun Jue-Qiong Xu quentin liu Zi-Jie Long Department of Hematology The Third Affiliated HospitalSun Yat-sen UniversityInstitute of HematologySun Yat-sen UniversityGuangzhouChina Department of Nephrology The Third Affiliated Hospitalun Yat-sen UniversityGuangzhouChina Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types,including hematopoietic ***,acute myeloid leukemia(AML)is a heterogeneous disease and there is stll a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage.

关键词： myeloid acute leukemia

The suppression of cervical cancer ferroptosis by macrophages:The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2645-2662页

作者： Yanlin Luo Yibing Chen Huan Jin Benxin Hou Hongsheng Li Xiang Li Lingfeng liu Yuan Zhou Yonghua Li Yong Sang Song quentin liu Zhengzhi Zou Department of Gynecologic Oncology the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450001China MOE Key Laboratory of Laser Life Science&Institute of Laser Life Science Guangdong Provincial Key Laboratory of Laser Life ScienceCollege of BiophotonicsSouth China Normal UniversityGuangzhou 510631China Institute of Clinical Pharmacology School of Basic Medical ScienceAcademy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Genetic and Prenatal Diagnosis Center Department of Gynecology and ObstetricsFirst Affiliated HospitalZhengzhou UniversityZhengzhou 450001China Department of General Surgery the Third People's Hospital of Hainan ProvinceSanya 572000China Department of Breast Surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China Department of Obstetrics and Gynecology Cancer Research InstituteCollege of MedicineSeoul National UniversitySeoul 03080South Korea State Key Laboratory of Oncology in South China Cancer CenterSun Yat-sen UniversityGuangzhou 510631China Guangzhou Key Laboratory of Spectral Analysis and Functional Probes College of BiophotonicsSouth China Normal UniversityGuangzhou 510631China

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer ***-associated macrophages(TAMs)play a key role in promoting tumor malignant progression and therapy ***,the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains *** study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in *** have been found to suppress cervical cancer cells ***,macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer *** cancer cells,miRNA-660-5p attenuates ALOX15 expression to inhibit ***,the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 ***,in clinical cervical cancer cases,ALOX15 is negatively associated with macrophages infiltration,which also raises the possibility that macrophages reduce ALOX15 levels in cervical ***,both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical ***,this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

关键词： Cervical cancer Tumor-associated macrophage ALOX15 Ferroptosis Exosome miRNA-660-5p Macrophages infiltration STAT6

Nuclear Aurora kinase A triggers programmed death-ligand 1-mediated immune suppression by activating MYC transcription in triple-negative breast cancer

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Cancer Communications 2021年第9期41卷 851-866页

作者： Shulan Sun Wei Zhou Xiaoxi Li Fei Peng Min Yan Yajing Zhan Fan An Xiaoyan Li Yunyong liu quentin liu Haozhe Piao Central Laboratory Cancer Hospital of China Medical UniversityDalian Medical University Clinical Oncology CollegeLiaoning Cancer Hospital&InstituteShenyangLiaoning 110042P.R.China Institute of Cancer Stem Cell Dalian Medical UniversityDalianLiaoning 116044P.R.China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Pathology Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and instituteShenyangLiaoning 110042P.R.China Department of Cancer Prevention and Treatment Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyangLiaoning 110042P.R.China Department of Neurosurgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyangLiaoning 110042P.R.China

Background:Increasing studies have reported that oncogenes regulate components of the immune system,suggesting that this is a mechanism for *** kinase A(AURKA),a serine/threonine kinase,is involved in cell mitosis and is essential for tumor cell proliferation,metastasis,and drug ***,the mechanism by which AURKA is involved in immune response regulation is ***,this study aimed to investigate the role of AURKA in immune regulation in triple-negative breast cancer(TNBC).Methods:Peripheral blood mononuclear cells(PBMCs)were co-cultured with TNBC *** xCELLigence Real-Time Cell Analyzer-MP system was used to detect the killing efficiency of immune cells on TNBC *** expression of immune effector molecules was tested by quantitative real-time polymerase chain reaction(qRT-PCR)to evaluate immune ***,to validate AURKA-regulated immune response in vivo,4T1 murine breast cancer cell line with AURKA overexpression or downregulation was engrafted into BALB/c *** distribution and proportion of immune cells in tumors were further evaluated by immunohistochemistry and flow ***:Downregulation of AURKA in TNBC cells increased immune response by activating CD8^(+)T cell proliferation and *** rather than cytoplasmic AURKA-derived programmed death-ligand 1(PD-L1)expression was independent of its kinase *** investigations showed that nuclear AURKA increased PD-L1 expression via an MYC-dependent ***-L1 overexpression mostly reversed AURKA silencing-induced expression of immune effector molecules,including interleukin-(IL-2),interferon-γ(IFN-γ),and ***,AURKA expression was negatively correlated with the enrichment and activity of tumor-infiltrating CD8^(+)T cells in 4T1 engrafted BALB/c mouse ***:Nuclear AURKA elevated PD-L1 expression via an MYCdependent pathway and contributed to immune evasion in *** targeting nuclear AU

关键词： Aurora kinase A immune evasion immunotherapy MYC programmed death-ligand 1 triplenegative breast cancer

Differentiation therapy:a promisingstrategy for cancer treatment

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Chinese Journal of Cancer 2016年第1期35卷 1-3页

作者： Min Yan quentin liu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center510060 GuangzhouGuangdongP.R.China Institute of Cancer Stem Cell Cancer CenterDalian Medical University116044 DalianLiaoningP.R.China

Poor differentiation is an important hallnnark of cancer cells,and differentiation therapy holds great promise for cancer *** restoration of IkB kinase a(IKKa)leads to the differentiation of nasopharyngeal carcinoma cells with reduced *** findings by Yan et *** the polycomb protein enhancer of zeste homologue2(EZH2)as a target for intervention.

关键词： Differentiation therapy, Cancer treatment, IkB kinase α

Targeted therapy: tailoring cancer treatment

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Chinese Journal of Cancer 2013年第7期32卷 363-364页

作者： Min Yan quentin Qiang liu State Key Laboratory of Oncology in South China Research Department Sun Yat-sen University Cancer Center Institute of Cancer Stem Cell Cancer Center Dalian Medical University

Targeted therapies include small-molecule inhibitors and monoclonal antibodies, have made treatment more tumor-specific and less toxic, and have opened new possibilities for tailoring cancer treatment. Nevertheless, there remain several challenges to targeted therapies, including molecular identification, drug resistance, and exploring reliable biomarkers. Here, we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases, PI3K/mTOR signaling, FOXO-FOXM1 axis, and MDM2/MDM4-p53 interaction. Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

关键词：癌症治疗靶向治疗剪裁单克隆抗体生物标志物分子鉴定信号通路分子机制

CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer

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Cancer Communications 2021年第2期41卷 121-139页

作者： Ailin Chen Shijun Wen Fang liu Zijian Zhang Meiling liu Yuanzhong Wu Bin He Min Yan Tiebang Kang Eric W-F Lam Zifeng Wang quentin liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China Institute of Cancer Stem Cell Dalian Medical UniversityDalianLiaoning 116044P.R.China Department of Surgery and Cancer Imperial College LondonW120NNLondonUK

Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse *** selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of ***,identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic ***:Here,we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with ***,we performed competitive growth assays,colony formation assays,cell viability assays,apoptosis assays,and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin(GSG2)depletion or inhibition with *** mechanistic studies,immunofluorescence was used to detect the state of microtubules and the localization of Aurora-B and mitotic centromere-associated kinesin(MCAK).Results:Among the hits,we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of *** studies showed that co-treatment with Aurora-A and Haspin inhibitors abolished the recruitment of Aurora-B and mitotic centromere-associated kinesin(MCAK)to centromeres which were associated with excessive microtubule depolymerization,kinetochore-microtubule(KT-MT)attachment failure,and severe mitotic *** further showed that the combination of MLN8237 and the Haspin inhibitor CHR-6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor ***:These findings establish Haspin as a synthetic lethal targe

关键词： alisertib Aurora-A breast cancer CHR-6494 CRISPR/Cas9 screening haspin kinetochoremicrotubule mitotic centromere-associated kinesin synthetic lethal xenograft

SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1265-1279页

作者： Yuesheng Lv Wenjing Zhang Jinyao Zhao Bing Sun Yangfan Qi Haoyu Ji Chaoqun Chen Jinrui Zhang Junxiu Sheng Taishu Wang Daniel Dominguez Han liu quentin liu Songshu Meng Xiaoling Li Yang Wang Second Affiliated Hospital Institute of Cancer Stem CellDalian Medical UniversityDalianChina Department of Thoracic Surgery First Affiliated HospitalDalian Medical UniversityDalianChina Department of Radiation Oncology First Affiliated HospitalDalian Medical UniversityDalianChina Department of Pharmacology University of North Carolina at Chapel HillChapel HillNCUSA Signal Transduction Laboratory National Institute of Environmental Health SciencesResearch Triangle ParkNCUSA

Alternative splicing is a critical process to generate protein ***,whether and how alternative splicing regulates autophagy remains largely *** we systematically identify the splicing factor SRSF1 as an autophagy ***,SRSF1 inhibits autophagosome formation by reducing the accumulation of LC3-ⅡI and numbers of autophagosomes in different cell ***,SRSF1 promotes the splicing of the long isoform of Bcl-x that interacts with Beclinl,thereby dissociating the Beclin1-PIK3C3 *** addition,SRSF1 also directly interacts with PIK3C3 to disrupt the interaction between Beclinl and ***,the decrease of SRSF1 stabilizes the Beclinl and PIK3C3 complex and activates ***,SRSF1 can be degraded by starvation-and oxidative stresses-induced autophagy through interacting with LC3-Ⅱ,whereas reduced SRSF1 further promotes *** positive feedback is critical to inhibiting Gefitinib-resistant cancer cell progression both in vitro and in ***,the expression level of SRSF1 is inversely correlated to LC3 level in clinical cancer *** study not only provides mechanistic insights of alternative splicing in autophagy regulation but also discovers a new regulatory role of SRSF1 in tumorigenesis,thereby offering a novel avenue for potential cancer therapeutics.

关键词： Beclin1 Beclin thereby