Dev Proj 2: Optical Dissection of a Lung Cancer Tumor Suppressor Gene

开发项目 2：肺癌肿瘤抑制基因的光学解剖

• 批准号: 7287015
• 负责人: Adam I. Marcus
• 金额: $ 3.82万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287015
• 关键词: 3-Dimensional; A549; Abnormal Cell; Actin-Binding Protein; Actins; Animals; Appearance; Area; Biological Assay; Biological Markers; Blinded; Breast; Breast Carcinoma; Cancer Patient; Carcinoma; Cell Polarity; Cell membrane; Cells; Cessation of life; Clinical Trials; Cytochalasin D; Cytoskeleton; Data; Defect; Diffuse; Dissection; Doctor of Philosophy; E-Cadherin; E-Cadherin Staining Method; Environment; Epithelial; Epithelial Cells; Event; Fibronectins; Figs - dietary; Fluorescence; Fluorescence Recovery After Photobleaching; Future; Galactose; Goals; Golgi Apparatus; Green Fluorescent Proteins; Growth; Human; Image; Image Analysis; Immunohistochemistry; In Situ; Incubated; Invaded; Invasive; Ions; Kinetics; Lasers; Life; Localized; Lung Neoplasms; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Matrigel Invasion Assay; Mediating; Mesenchymal; Microscope; Modeling; Motor; Movement; Mutate; Mutation; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Nuclear; Optics; Paraffin Embedding; Pathologist; Pathology; Patients; Pharmaceutical Preparations; Phase-Contrast Microscopy; Phenotype; Phosphotransferases; Photobleaching; Pilot Projects; Platelet-Derived Growth Factor; Play; Positioning Attribute; Primary Neoplasm; Proliferating; Protein Overexpression; Proteins; Rate; Recovery; Recruitment Activity; Role; STK11 gene; Sample Size; Sampling; Series; Signal Transduction; Signaling Molecule; Slide; Small Interfering RNA; Solutions; Specimen; Staining method; Stains; Testing; Therapeutic; Time; Tissue Microarray; Tissues; Tolonium chloride; Transferase; Tumor Cell Invasion; Tumor Suppressor Genes; Tumor-Suppressor Gene Inactivation; Vimentin; base; cancer cell; cell fixing; cell motility; cellular imaging; data management; depolymerization; fluorophore; image processing; in vivo; interest; migration; mutant; polarized cell; polymerization; programs; research study; spatiotemporal; time use; tissue fixing; translational study; tumor; wound

Pilot Project 2: Optical dissection of a lung cancer tumor suppressor gene PI: Adam I. Marcus, PhD Tumor metastasis is the primary cause of patient death in almost all cancers. Attempts at developing a therapeutic strategy that can block metastasis is limited by our understanding of how stationary cancer cells transform into malignant carcinomas. It is already known that one key step is the inactivation of tumor suppressor genes, which allows cancer cells to continuously proliferate and eventually metastasize. In nonsmall cell lung cancer (NSCLC) the tumor suppressor gene, LKB1 is mutated in 30% of all primary tumors. A series of studies in normal epithelial cells implicate LKB1 as a master regulator of epithelial cell polarity raising the possibility that in NSCLC, LKB1 loss triggers an aberrant cell polarity program and subsequent cell invasion. Interestingly, our preliminary data implicate LKB1 in NSCLC motility and migration; therefore, we will test the hypothesis that LKB1 loss in NSCLC eliminates the activity of this suppressor and triggers cancer cell invasion. These studies will rely on live cell confocal imaging to determine how LKB1 mediates NSCLC invasion. Importantly, these mechanistic initiatives will be bridged with more translational studies investigating the impact of LKB1 loss on cancer cell invasion

试点项目2：光学解剖肺癌肿瘤抑制基因PI：Adam I.Marcus，PhD 肿瘤转移是几乎所有癌症患者死亡的主要原因。尝试开发一种 阻止转移的治疗策略受到我们对静止癌细胞如何 转化为恶性肿瘤。已经知道，其中一个关键步骤是灭活肿瘤 抑制基因，它允许癌细胞持续增殖并最终转移。在非小规模 细胞肺癌(NSCLC)抑癌基因LKB1在所有原发肿瘤中有30%发生突变。一个 对正常上皮细胞的一系列研究表明LKB1是上皮细胞极性升高的主要调节因子 在非小细胞肺癌中，LKB1丢失触发异常细胞极性编程和后续细胞的可能性 入侵。有趣的是，我们的初步数据表明LKB1与非小细胞肺癌的运动和迁移有关；因此，我们将 验证LKB1在非小细胞肺癌中丢失会消除该抑制因子的活性并触发癌细胞的假设 入侵。这些研究将依靠活细胞共聚焦成像来确定LKB1是如何介导NSCLC的 入侵。重要的是，这些机械性的倡议将与更多的翻译研究相结合 LKB1缺失对癌细胞侵袭的影响