Dataset Information

Proteomic analysis of extracellular vesicles identifies CDCP1 as critical metastasis-related glycoprotein in lung cancer

ABSTRACT: Lung cancer is the most prevalent malignancy worldwide, with metastasis causing over 90% of fatalities. Recent studies have demonstrated the pivotal role of extracellular vesicles (EVs) and glycoproteins in tumor progression. In this study, we compared the glycoproteome of EVs from 95C (low metastatic) and 95D (high metastatic) lung cancer cells to discover key targets in metastasis. Through coupling lectin affinity chromatography with quantitative proteomics, 1562 glycoproteins were identified. Compared to 95C EVs, 23 glycoproteins were significantly upregulated more than 20-fold in 95D EVs, including CDCP1, TNC, NCAM2, and ITGA4. CUB-domain containing protein 1 (CDCP1) was upregulated 143-fold in 95D EVs, which is significantly correlated with poor prognosis of lung cancer patients in the TCGA database. We then generated CDCP1 knockout (KO) 95D cell lines and revealed that the absence of CDCP1 reduced cell migration ability, which was also confirmed by EVs and cell co-culture experiments. We further performed Ti4+-IMAC based phosphoproteomic analysis to investigate the changes of signaling pathways in CDCP1 KO cell lines. 147 differentially expressed phosphoproteins were revealed, which involve in cell adhesion, cytoskeletal regulation, and ErbB signaling. Verification experiments confirmed that the levels of phosphorylated SRC and JUN proteins, markers of ErbB signaling pathway, were decreased 5.5-fold and 4.2-fold, respectively, indicating that CDCP1 can promote cell migration through the ErbB signaling pathway. Our data demonstrate that glycoprotein CDCP1 was selectively packed into EVs and potentially contributed to cancer metastasis, which is a critical target for anti-metastasis research and cancer therapy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

SUBMITTER: Lu Zhang

LAB HEAD: Hua Xiao

PROVIDER: PXD064331 | Pride | 2025-08-04

REPOSITORIES: Pride

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			Action	DRS
	95D-CDCP1-IP-HILIC.raw	Raw
	95D-CDCP1-IP-HILIC.xlsx	Xlsx

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Publications

Proteomic Analysis of Extracellular Vesicles Identifies CDCP1 as Critical Metastasis-Related Glycoprotein in Lung Cancer.

Zhang Lu L Wu Yan Y Li Suntao S Guo Miao M Zhao Jiaqi J Cao Chengxi C Zhang Yan Y Xiao Hua H

Journal of extracellular vesicles 20250701 7

Lung cancer is the most prevalent malignancy worldwide, with the majority of fatalities attributed to metastasis. Recent studies have demonstrated the pivotal role of extracellular vesicles (EVs) and glycoproteins in tumor progression. In this study, we compared the glycoproteome of EVs from 95C (low metastatic) and 95D (high metastatic) lung cancer cells to discover key targets in metastasis. Through coupling lectin affinity chromatography with quantitative proteomics, 1562 glycoproteins were i ...[more]

PMID: 40693605

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