The mechanism and function of cell competition in tumors

肿瘤细胞竞争的机制和功能

• 批准号: 9319656
• 负责人: Wei Li
• 金额: $ 17.54万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-19 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9319656
• 关键词: Affect; Apoptosis; Apoptosis Inhibitor; Area; Biological; Biological Process; Bromodeoxyuridine; CASP3 gene; Cancer Biology; Candidate Disease Gene; Cell Adhesion; Cell Communication; Cell Death; Cell Proliferation; Cell physiology; Cells; Cellular Structures; Cellular biology; Characteristics; Cleaved cell; Clone Cells; Communities; Consult; Core Facility; Cytoskeleton; Development; Development Plans; Environment; Evolution; Faculty; Fostering; Gene Expression; Gene Expression Profiling; Genes; Genetic Variation; Goals; Grant; Human; Imagery; Immune; Immune signaling; Immunohistochemistry; Immunologic Monitoring; In Vitro; Infiltration; Injectable; K22 Award; Knowledge; Lead; Malignant Neoplasms; Manuscripts; Mediating; Mediation; Mediator of activation protein; Memorial Sloan-Kettering Cancer Center; Mentors; Mesothelioma; Methods; Modeling; Molecular; Monitor; Movement; Mus; Neurilemmoma; Nude Mice; Oncoproteins; Pathway interactions; Persons; Physiological Processes; Population; Positioning Attribute; Process; Public Health; RNA Interference; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Subjects; Resources; Sampling; Secure; Signal Transduction; Staining method; Stains; TdT-Mediated dUTP Nick End Labeling Assay; Techniques; Testing; Therapeutic; Time; Tumor Suppression; United States National Institutes of Health; Work; Writing; base; cancer cell; career; career development; cell growth; diagnostic biomarker; differential expression; epigenetic variation; experimental study; fitness; high risk; immunoreaction; improved; in vivo; meningioma; mutant; neoplastic cell; novel diagnostics; overexpression; programs; public health relevance; response; senescence; skills; subcutaneous; tenure track; therapeutic target; tool; treatment response; tumor; tumor growth; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): My long-term career goal is to secure a tenure-track faculty position and establish an independent research program in the area of cancer cell biology. I propose a three-year career development plan that will enable me to become a successful independent research investigator. In this proposed research, I will focus on understanding the mechanism and function of cell competition in tumors by achieving three specific aims: (1) to determine if differential YAP expression in NF2 mutant tumor cells can induce cell competition; (2) to identify mediators in the clonal dominance process induced by differential YAP expression; and (3) to determine the impact of the interaction between tumor cells differentially expressing YAP on tumorigenesis. The main approach in this study will be tumor cell clonal dominance models. Results from this proposed research will provide mechanistic and functional indications of the competitive interaction between tumor cells. Moreover, identified molecular mediators and effectors of the competitive interaction might be developed into diagnostic markers or therapeutic targets since cell competition could modulate tumor progression and therapeutic response. This proposed career development plan is based on my past unique scientific history, which makes me an ideal person to pursue this subject. Because this project is in the early stages of development, management of high risk aspects of the proposed work, such as establishment of models and research tools, is anticipated to be technique-challenging. In seeking a K22 award, I aim to gain additional skills in studying cellular interactions in cancer. These skills will be obtained through attending courses and consulting/collaborating with related experts. Dr. Filippo Giancotti's lab, a well-known research program in studying cell adhesion and signaling in cancer biology, as well as MSKCC, an ideal environment with state-of- the-art core facilities and a highly interactive scientific community, provide me unique recourses for my research and other career development activities to strengthen my professional skills in: grant and manuscript writing, presentation, the application process and negotiations for tenure track positions, mentoring and lab management. The K22 award would provide me with protected time critical to strengthen the new research subject and would foster my interaction with the diverse expertise in this community, facilitate my maturation as an independent researcher, and enable a smooth transition toward my independent career.

描述（由申请人提供）：我的长期职业目标是获得终身教职，并在癌细胞生物学领域建立独立的研究计划。我提出了一个为期三年的职业发展计划，使我能够成为一个成功的独立研究调查员。在本研究中，我将通过以下三个具体目标来理解肿瘤细胞竞争的机制和功能：（1）确定NF 2突变肿瘤细胞中差异雅普表达是否能诱导细胞竞争;（2）鉴定差异雅普表达诱导的克隆优势过程中的介质;以及（3）确定差异表达雅普的肿瘤细胞之间的相互作用对肿瘤发生的影响。本研究的主要方法是肿瘤细胞克隆优势模型。这项研究的结果将为肿瘤细胞之间的竞争性相互作用提供机制和功能指标。此外，由于细胞竞争可以调节肿瘤的进展和治疗反应，因此鉴定出的竞争相互作用的分子介质和效应物可能被开发成诊断标志物或治疗靶点。这个职业发展计划是基于我过去独特的科学史，这使我成为追求这一主题的理想人选。由于该项目正处于开发的早期阶段，因此对拟议工作的高风险方面（例如建立模型和研究工具）的管理预计将具有技术挑战性。在寻求K22奖，我的目标是获得额外的技能，研究细胞 癌症中的相互作用。这些技能将通过参加课程和咨询/与相关专家合作获得。Filippo Giancotti博士的实验室是一个研究癌症生物学中细胞粘附和信号传导的著名研究项目，MSKCC是一个拥有最先进的核心设施和高度互动的科学社区的理想环境，为我的研究和其他职业发展活动提供了独特的资源，以加强我在以下方面的专业技能：赠款和手稿写作，演示文稿，申请过程和终身职位的谈判，指导和实验室管理。K22奖将为我提供保护的时间，这对加强新的研究课题至关重要，并将促进我与这个社区的各种专业知识的互动，促进我作为一名独立研究人员的成熟，并使我能够顺利过渡到独立的职业生涯。