Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells.
Elijah N McCoolTian XuWenrong ChenNicole C BellerScott M NolanAmanda B HummonXiaowen LiuLiangliang SunPublished in: Science advances (2022)
Understanding cancer metastasis at the proteoform level is crucial for discovering previously unknown protein biomarkers for cancer diagnosis and drug development. We present the first top-down proteomics (TDP) study of a pair of isogenic human nonmetastatic and metastatic colorectal cancer (CRC) cell lines (SW480 and SW620). We identified 23,622 proteoforms of 2332 proteins from the two cell lines, representing nearly fivefold improvement in the number of proteoform identifications (IDs) compared to previous TDP datasets of human cancer cells. We revealed substantial differences between the SW480 and SW620 cell lines regarding proteoform and single amino acid variant (SAAV) profiles. Quantitative TDP unveiled differentially expressed proteoforms between the two cell lines, and the corresponding genes had diversified functions and were closely related to cancer. Our study represents a pivotal advance in TDP toward the characterization of human proteome in a proteoform-specific manner, which will transform basic and translational biomedical research.
Keyphrases
- endothelial cells
- papillary thyroid
- amino acid
- amyotrophic lateral sclerosis
- induced pluripotent stem cells
- mass spectrometry
- pluripotent stem cells
- squamous cell carcinoma
- metastatic colorectal cancer
- small cell lung cancer
- gene expression
- lymph node metastasis
- high resolution
- dna methylation
- small molecule
- childhood cancer
- transcription factor
- binding protein
- drug induced