Identification of Nidogen 1 as a lung metastasis protein through secretome analysis.
Identification of Nidogen 1 as a lung metastasis protein through secretome analysis.
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DOI：
10.1101/gad.301937.117
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发表时间：
2017-07-15
影响因子：
10.5
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Alečković M;Wei Y;LeRoy G;Sidoli S;Liu DD;Garcia BA;Kang Y
Alečković等人鉴定了新的候选肺转移蛋白，包括Nidogen 1（NID 1），其被证实促进乳腺癌和黑色素瘤的肺转移，并且其表达与不良临床结果相关。在肿瘤向不同靶器官转移的过程中，分泌蛋白在介导肿瘤-间质相互作用中起关键作用。为了全面分析参与肺转移的分泌蛋白，我们应用基于定量质谱的蛋白质组学，并确定了392个乳腺癌衍生和302个黑色素瘤衍生的蛋白质，这些蛋白质是从高肺转移细胞中分泌的。在多个癌症临床数据集中，癌症特异性肺转移分泌组特征（LMSS）显示出显著的预后价值。此外，我们观察到乳腺癌和黑色素瘤的LMSS之间富集途径的显著重叠，尽管特定蛋白质的总体重叠较小，这表明共同的生物过程由不同的蛋白质执行，以使两种癌症类型转移到肺部。在新的候选肺转移蛋白中，Nidogen 1（NID 1）被证实促进乳腺癌和黑色素瘤的肺转移，并且其表达与不良的临床结果相关。体外功能分析进一步揭示了NID 1的多种促转移功能，包括增强癌细胞迁移和侵袭，促进与内皮的粘附并破坏其完整性，以及改善血管形成能力。NID 1作为一种分泌型促转移蛋白，有望成为乳腺癌和黑色素瘤疾病进展的新生物标志物和治疗靶点。
Alečković et al. identified novel candidate lung metastasis proteins, including Nidogen 1 (NID1), which was confirmed to promote lung metastasis of breast cancer and melanoma and whose expression is correlated with poor clinical outcomes. 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.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.9
作者：
BROOKS, PC;STROMBLAD, S;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
19.6
作者：
AUMAILLEY, M;BATTAGLIA, C;FOX, JW
通讯作者：
FOX, JW
DOI：
10.1093/bioinformatics/btp536
发表时间：
2009-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Binns D;Dimmer E;Huntley R;Barrell D;O'Donovan C;Apweiler R
通讯作者：
Apweiler R
影响因子：
3.8
作者：
Gyoerffy, Balazs;Lanczky, Andras;Szallasi, Zoltan
通讯作者：
Szallasi, Zoltan