Quantitative top-down proteomics reveals significant differences in histone proteoforms between metastatic and nonmetastatic colorectal cancer cells

ABSTRACT: As one of the leading causes of cancer deaths worldwide, colorectal cancer (CRC) development is closely associated with the accumulation of both genetic and epigenetic alterations. Many efforts have been made to investigate the role of epigenetic modifications in CRC metastasis. In this work, we present the first quantitative top-down proteomics study focusing on histone proteoforms between metastatic (SW620) and nonmetastatic (SW480) CRC cells to reveal potentially critical histone proteoforms in CRC metastasis. We isolated histone proteins from CRC cells, separated them by sodium dodecyl-sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), recovered each histone protein from the gel, and analyzed them by capillary zone electrophoresis (CZE)-tandem mass spectrometry (MS/MS). A total of 230 histone proteoforms were quantified in SW480 and SW620 cell lines, among which 34 proteoforms were significantly altered in abundance in the metastatic cells, indicating a significant transformation of histone proteoforms during metastasis. We observed a significant increase in abundance of all nine differentially expressed histone H4 proteoforms in metastatic SW620 cells compared to SW480 cells, while differentially expressed proteoforms of other histone proteins display diversified expression patterns. Additionally, two histone H2A proteoforms with a combination of N-terminal acetylation and phosphorylation were upregulated in the metastatic CRC cells. These differentially expressed histone proteoforms could be novel proteoform biomarkers of CRC metastasis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Liangliang Sun  

LAB HEAD: Liangliang Sun

PROVIDER: PXD060160 | Pride | 2025-11-21

REPOSITORIES: Pride