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: 10209266
• 负责人: MARK A. MC NIVEN
• 金额: $ 36.37万
• 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/10209266
• 关键词: 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; Investigation; Lead; 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

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.

肺癌是美国与癌症有关的主要原因，超过15万 美国人每年死于肺癌。尽管我们最好的治疗方法，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理解不足，几乎不可避免地会导致 致肺癌死亡。因此，更好地理解调节转移的机制将使我们能够获得 对疾病基础的更深入的见解，以哪种治疗转移性肺癌的新型治疗策略 可以开发和测试。根据我们的初步研究，我们认为与自噬相关基因 通过新的线粒体相关的线粒体在调节肺癌转移中起关键作用 机制。该提案的主要目标是确定是否操纵此表达 基因或其线粒体相关功能可以抑制肺癌的传播。因此，我们的研究 不仅揭示了一种新的肺癌基本机制，而且具有转化潜力。因为有 每年在全球约有200万新的肺癌病例（世界卫生组织统计数据），我们的研究可能 对公共卫生有重大影响。