Systems Biology Ireland, School of Medicine, University College Dublin, Dublin, Ireland.
Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Sci Data. 2024 Oct 10;11(1):1111. doi: 10.1038/s41597-024-03965-y.
Neurotrophic receptor tyrosine kinases (TrkA, TrkB, TrkC), despite their homology, contribute to the clinical heterogeneity of the childhood cancer neuroblastoma. TrkA expression is associated with low-stage disease and is often seen with spontaneous tumour regression. Conversely, TrkB is present in unfavourable neuroblastomas that often harbour amplification of the MYCN oncogene. The role of TrkC is less clearly defined, although some studies suggest its association with a favourable outcome. Understanding the differences in activity of Trk receptors that drive divergent clinical phenotypes as well as the influence of MYCN amplification on downstream Trk receptor signalling remains poorly understood. Here, we present a comprehensive label-free mass spectrometry-based total proteomics and phosphoproteomics dataset (432 raw files with FragPipe search outputs; available on PRIDE with accession number PXD054441) where we identified and quantified 4,907 proteins, 16,744 phosphosites and 5,084 phosphoproteins, derived from NGF/BDNF/NT-3 treated TrkA/B/C-overexpressing neuroblastoma cells with differential MYCN status. Analysing our dataset offers valuable insights into TrkA/B/C receptor signalling in neuroblastoma and its modulation by MYCN status; and holds potential for advancing therapeutic strategies in this challenging childhood cancer.
神经营养受体酪氨酸激酶(TrkA、TrkB、TrkC)尽管具有同源性,但对儿童癌症神经母细胞瘤的临床异质性有贡献。TrkA 的表达与低分期疾病相关,常伴有自发性肿瘤消退。相反,TrkB 存在于不良的神经母细胞瘤中,这些肿瘤通常存在 MYCN 癌基因的扩增。TrkC 的作用不太明确,尽管一些研究表明它与有利的结果有关。了解驱动不同临床表型的 Trk 受体活性差异以及 MYCN 扩增对下游 Trk 受体信号转导的影响仍然知之甚少。在这里,我们提出了一个全面的无标签基于质谱的总蛋白质组学和磷酸蛋白质组学数据集(432 个原始文件与 FragPipe 搜索输出;可在 PRIDE 上获得,访问号为 PXD054441),我们从 NGF/BDNF/NT-3 处理的过表达 TrkA/B/C 的神经母细胞瘤细胞中鉴定和定量了 4907 种蛋白质、16744 个磷酸化位点和 5084 个磷酸化蛋白质,这些细胞具有不同的 MYCN 状态。分析我们的数据集为神经母细胞瘤中 TrkA/B/C 受体信号及其受 MYCN 状态调节提供了有价值的见解;并有可能为这种具有挑战性的儿童癌症推进治疗策略。