Identification of Tyrosine-Phosphorylated Proteins Associated with Lung Cancer Metastasis using Label-Free Quantitative Analyses

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• 作者：Hsin-Yi Wu ; Vincent S. Tseng ; Lien-Chin Chen ; Hui-Yin Chang ; I-Chi Chuang ; Yeou-Guang Tsay ; Pao-Chi Liao
• 刊名：Journal of Proteome Research
• 出版年：2010
• 出版时间：August 6, 2010
• 年：2010
• 卷：9
• 期：8
• 页码：4102-4112
• 全文大小：468K
• 年卷期：v.9,no.8(August 6, 2010)
• ISSN：1535-3907

文摘

Lung cancer is a lethal disease, and early metastasis is the major cause of treatment failure and cancer-related death. Tyrosine phosphorylated (P-Tyr) proteins are involved in the invasive and metastatic behavior of lung cancer; however, only a limited number of targets were identified. We attempt to characterize P-Tyr proteins and events involved in the metastatic process. In a previous work, we have developed a strategy for identification of protein phosphorylation. Here, this strategy was used to characterize the tyrosine phosphoproteome of lung cancer cells that have different invasive abilities (CL1-0 vs. CL1-5). Using our analytical strategy, we report the identification of 335 P-Tyr sites from 276 phosphoproteins. Label-free quantitative analysis revealed that 36 P-Tyr peptides showed altered levels between CL1-0 and CL1-5 cells. From this list of sites, we extracted two novel consensus sequences and four known motifs for specific kinases and phosphatases including EGFR, Src, JAK2, and TC-PTP. Protein−protein interaction network analysis of the altered P-Tyr proteins illustrated that 11 proteins were linked to a network containing EGFR, c-Src, c-Myc, and STAT, which is known to be related to lung cancer metastasis. Among these 11 proteins, 7 P-Tyr proteins have not been previously reported to be associated with lung cancer metastasis and are of greatest interest for further study. The characterized tyrosine phosphoproteome and altered P-Tyr targets may provide a better comprehensive understanding of the mechanisms of lung cancer invasion/metastasis and discover potential therapies.

Keywords:

tyrosine phosphorylation; lung cancer metastasis; mass spectrometry; immunoaffinity enrichment; label-free quantitative analysis