Identification of Nidogen 1 as a lung metastasis protein through secretome analysis.

TitleIdentification of Nidogen 1 as a lung metastasis protein through secretome analysis.
Publication TypeJournal Article
Year of Publication2017
AuthorsAlečković, M, Wei, Y, LeRoy, G, Sidoli, S, Liu, DD, Garcia, BA, Kang, Y
JournalGenes Dev
Volume31
Issue14
Pagination1439-1455
Date Published2017 07 15
ISSN1549-5477
KeywordsBreast Neoplasms, Cell Line, Tumor, Cell Movement, Female, Humans, Lung Neoplasms, Melanoma, Membrane Glycoproteins, Prognosis
Abstract

<p>Secreted proteins play crucial roles in mediating tumor-stroma interactions during metastasis of cancer to different target organs. To comprehensively profile secreted proteins involved in lung metastasis, we applied quantitative mass spectrometry-based proteomics and identified 392 breast cancer-derived and 302 melanoma-derived proteins secreted from highly lung metastatic cells. The cancer-specific lung metastasis secretome signatures (LMSSs) displayed significant prognostic value in multiple cancer clinical data sets. Moreover, we observed a significant overlap of enriched pathways between the LMSSs of breast cancer and melanoma despite an overall small overlap of specific proteins, suggesting that common biological processes are executed by different proteins to enable the two cancer types to metastasize to the lung. Among the novel candidate lung metastasis proteins, Nidogen 1 (NID1) was confirmed to promote lung metastasis of breast cancer and melanoma, and its expression is correlated with poor clinical outcomes. In vitro functional analysis further revealed multiple prometastatic functions of NID1, including enhancing cancer cell migration and invasion, promoting adhesion to the endothelium and disrupting its integrity, and improving vascular tube formation capacity. As a secreted prometastatic protein, NID1 may be developed as a new biomarker for disease progression and therapeutic target in breast cancer and melanoma.</p>

DOI10.1101/gad.301937.117
Alternate JournalGenes Dev.
PubMed ID28827399
PubMed Central IDPMC5588926
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
R01 CA134519 / CA / NCI NIH HHS / United States
R01 CA141062 / CA / NCI NIH HHS / United States