Investigation of a mitochondria-associated metastasis regulatory mechanism

线粒体相关转移调控机制的研究

• 批准号: 10693170
• 负责人: MARK A. MC NIVEN
• 金额: $ 35.64万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693170
• 关键词: Ablation; American; Autophagocytosis; Autophagosome; Binding; Biological; Biology; Cancer Etiology; Cancer Patient; Cause of Death; Cessation of life; Data; Data Set; Disease; Future; Gene Expression; Genes; Genetic Transcription; Genetically Engineered Mouse; Goals; Growth; Invaded; Investigation; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Membrane; Mitochondria; Neoplasm Metastasis; Play; Process; Promoter Regions; Public Health; Regulation; Repression; Role; Testing; The Cancer Genome Atlas; Therapeutic; Tumor Suppressor Proteins; United States; World Health Organization; effective therapy; gene repression; improved; insight; migration; novel; novel therapeutic intervention; statistics; transcription factor; translational potential

Lung cancer is the leading cause of cancer-related death in the United States, and more than 150,000 Americans die of lung cancer each year. Despite our best treatment, efforts to cure lung cancer have failed in most cases, partly due to an insufficient understanding of the biology of metastasis, which almost inevitably leads to lung cancer death. Therefore, understanding better the mechanism regulating metastasis will allow us to gain deeper insights into the disease basis, on which novel therapeutic strategies for treating metastatic lung cancer can be developed and tested. On the basis of our preliminary studies, we posit that an autophagy related gene plays a critical role in the regulation of lung cancer metastasis through a novel mitochondria associated mechanism. The primary objectives of this proposal are to determine whether manipulating the expression of this gene or its mitochondria associated function can inhibit the dissemination of lung cancer. As such, our studies not only reveal a new basic mechanism for lung cancer, but have translational potentials. Because there are about 2 million new lung cancer cases each year globally (World Health Organization statistics), our studies may have a major impact on public health.

肺癌是美国癌症相关死亡的主要原因，超过 150,000 每年都有美国人死于肺癌。尽管我们采取了最好的治疗方法，但治愈肺癌的努力还是失败了 大多数情况下，部分原因是对转移生物学的了解不足，这几乎不可避免地导致 至肺癌死亡。因此，更好地了解调节转移的机制将使我们获得 更深入地了解疾病基础，在此基础上治疗转移性肺癌的新治疗策略 可以开发和测试。根据我们的初步研究，我们推测自噬相关基因 通过与肺癌相关的新型线粒体在调节肺癌转移中发挥关键作用 机制。该提案的主要目标是确定是否操纵此表达式 基因或其线粒体相关功能可以抑制肺癌的播散。因此，我们的研究 不仅揭示了肺癌的新基本机制，而且具有转化潜力。因为有 全球每年约有 200 万新发肺癌病例（世界卫生组织统计），我们的研究可能 对公众健康产生重大影响。