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.

项目总结