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Proteomics and Phosphoproteomics Profiling of PGCCs Reveal AARS as a Prognostic Biomarker for Colorectal Cancer

ABSTRACT: Considerable evidence suggests that polyploid giant cancer cells (PGCCs) can drive therapeutic resistance and relapse in colorectal cancer (CRC), with their abundance positively correlating with disease stage and malignancy. Given the significant implications of PGCCs, understanding their molecular characteristics could offer novel therapeutic strategies for CRC treatment. In this study, PGCCs are induced in HCT116 and LoVo colorectal cancer cell lines following cobalt chloride (CoCl₂) treatment, and then the differential expression patterns of proteins and phosphoproteins between PGCCs and regular cancer cells are investigated using a mass spectrometry-based proteomics approach coupled with tandem mass tag (TMT) labeling. The results indicate that the content and phosphorylation status of various proteins in PGCCs derived from cancer cells exhibit substantial alterations, with a notable focus on the concurrent upregulation of AARS phosphorylation at serine 399. These molecular signatures provide deeper insights into the biology of PGCCs and their contribution to CRC pathogenesis. Moreover, our findings highlight the potential of AARS as a novel prognostic biomarker and a promising therapeutic target for CRC patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiaoling Xu

PROVIDER: PXD067870 | iProX | Fri Aug 29 00:00:00 BST 2025

REPOSITORIES: iProX

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