Identification of Nidogen 1 as a lung metastasis protein through secretome analysis. Author Maša Alečković, Yong Wei, Gary LeRoy, Simone Sidoli, Daniel Liu, Benjamin Garcia, Yibin Kang Publication Year 2017 Type Journal Article Abstract 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. Keywords Humans, Female, Cell Line, Tumor, Cell Movement, Membrane Glycoproteins, Breast Neoplasms, Lung Neoplasms, Prognosis, Melanoma Journal Genes Dev Volume 31 Issue 14 Pages 1439-1455 Date Published 2017 Jul 15 ISSN Number 1549-5477 DOI 10.1101/gad.301937.117 Alternate Journal Genes Dev PMCID PMC5588926 PMID 28827399 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML