Quantitative top-down proteomics of human colorectal cancer cells and tumors

人类结直肠癌细胞和肿瘤的定量自上而下蛋白质组学

• 批准号: 10348194
• 负责人: Amanda B. Hummon
• 金额: $ 36.32万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-10 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348194
• 关键词: Amino Acid Sequence; Biological; Blood capillaries; Brain; Cancer Biology; Cell Line; Cells; Cessation of life; Colorectal Cancer; Communities; Consumption; Coupling; DNA; Data; Databases; Detection; Diagnosis; Disease; Electrophoresis; Fractionation; Gene Mutation; Genes; Genome; Hereditary Nonpolyposis Colorectal Neoplasms; Human; Immunoprecipitation; Inherited; Lead; Liquid Chromatography; MSH2 gene; Malignant Neoplasms; Methods; Mismatch Repair; Molecular; Mutation; Neoplasm Metastasis; Online Systems; Patients; Persons; Phase; Play; Post-Transcriptional Regulation; Post-Translational Protein Processing; Primary Neoplasm; Proteins; Proteome; Proteomics; Resources; Role; SW480; SW620; Sampling; System; Time; Tissues; Work; Zebrafish; analytical tool; cancer cell; capillary liquid chromatography; colon cancer cell line; colorectal cancer metastasis; gene repair; insight; lymph nodes; milligram; nano; neoplasm resource; neoplastic cell; novel; phosphoproteomics; protein expression; protein function; tandem mass spectrometry; tool; transcriptome; tumor

Project Summary It has been estimated that 145,600 people were diagnosed with colorectal cancer (CRC) and 51,020 deaths were predicted due to this disease in 2019 (https://seer.cancer.gov/statfacts/html/colorect.html). A better understanding of CRC at the molecular level will certainly lead to therapies that are more effective. The genome- level and transcriptome-level information cannot accurately reflect the protein-level information because post-transcriptional regulation can modulate protein expression and because post-translational modifications (PTMs) can influence protein function. Quantitative proteomic studies of CRC are vital. Many bottom-up proteomics studies have been completed on CRC cells and tumors, but limited information on proteoforms have been acquired due to low protein sequence coverages typically obtained from bottom-up proteomics. Different proteoforms from the same gene can have drastically different functions. We hypothesize that large-scale and quantitative top-down proteomics of human CRC cells and tumors will provide new insights into CRC, leading to better therapies. In this proposal, we will develop new analytical tools to boost the sensitivity and scale of top-down proteomics. The new tools will enable large-scale and quantitative top-down proteomics of CRC cells before and after metastasis as well as CRC tumors from patients with Lynch Syndrome. Results from this proposal are extremely important. The novel analytical tools will boost the sensitivity of top-down proteomics by tenfold and will be particularly useful for the proteomics community for large-scale top-down proteomics of mass-limited samples. Quantitative top-down proteomics of CRC cells before and after metastasis will generate an unprecedented resource for the cancer biology community to gain new insights into CRC metastasis. Quantitative top-down proteomics of the Lynch Syndrome tissues will elucidate the roles played by mutations and functions of DNA mismatch repair genes in Lynch Syndrome at the proteoform level.

项目摘要 据估计，有145,600人被诊断为结直肠癌（CRC） 预计2019年这种疾病导致了51,020例死亡 （https://seer.cancer.gov/statfacts/html/colecrect.html）。更好地理解CRC 分子水平肯定会导致更有效的疗法。基因组 - 水平和转录组级信息无法准确反映蛋白质级别 信息是因为转录后调节可以调节蛋白质的表达和 因为翻译后修饰（PTM）会影响蛋白质功能。 CRC的定量蛋白质组学研究至关重要。 许多自下而上的蛋白质组学研究已经在CRC细胞和肿瘤上完成，但是 由于低蛋白质序列，已获得有关蛋白质成型的信息有限 通常从自下而上的蛋白质组学获得的覆盖范围。来自 相同的基因可以具有截然不同的功能。我们假设大规模 人类CRC细胞和肿瘤的定量自上而下的蛋白质组学将提供 对CRC的新见解，导致更好的疗法。在此提案中，我们将发展 新的分析工具可提高自上而下的蛋白质组学的灵敏度和规模。新的 工具将使CRC细胞的大规模和定量自上而下的蛋白质组学之前 在转移以及来自林奇综合征患者的CRC肿瘤之后。结果 从该提议中非常重要。新颖的分析工具将提高 自上而下的蛋白质组学的敏感性是十倍，对 蛋白质组学社区，用于大规模自上而下的大规模限制样品蛋白质组学。 转移前后CRC细胞的定量自上而下的蛋白质组学将产生 癌症生物学社区的前所未有的资源，以获得新的见解 CRC转移。林奇综合征组织的定量自上而下的蛋白质组学将 阐明突变和DNA不匹配修复基因功能所起的作用 lynch综合征处于蛋白质相关水平。