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NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2021 Nov 13
PMID 34771457
Citations 8
Authors
Affiliations
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Abstract

(1) Background: Neuroblastomas (NBs) are the most common extracranial solid tumors of children. The amplification of the Myc-N proto-oncogene (MYCN) is a major driver of NB aggressiveness, while high expression of the neurotrophin receptor NTRK1/TrkA is associated with mild disease courses. The molecular effects of NTRK1 signaling in MYCN-amplified NB, however, are still poorly understood and require elucidation. (2) Methods: Inducible NTRK1 expression was realized in four NB cell lines with (IMR5, NGP) or without MYCN amplification (SKNAS, SH-SY5Y). Proteome and phosphoproteome dynamics upon NTRK1 activation by its ligand, NGF, were analyzed in a time-dependent manner in IMR5 cells. Target validation by immunofluorescence staining and automated image processing was performed using the three other NB cell lines. (3) Results: In total, 230 proteins and 134 single phosphorylated class I phosphosites were found to be significantly regulated upon NTRK1 activation. Among known NTRK1 targets, Stathmin and the neurosecretory protein VGF were recovered. Additionally, we observed the upregulation and phosphorylation of Lamin A/C (LMNA) that accumulated inside nuclear foci. (4) Conclusions: We provide a comprehensive picture of NTRK1-induced proteome and phosphoproteome dynamics. The phosphorylation of LMNA within nucleic aggregates was identified as a prominent feature of NTRK1 signaling independent of the MYCN status of NB cells.

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References
1.
Mosse Y, Laudenslager M, Longo L, Cole K, Wood A, Attiyeh E . Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008; 455(7215):930-5. PMC: 2672043. DOI: 10.1038/nature07261. View

2.
Nardella M, Guglielmi L, Musa C, Iannetti I, Maresca G, Amendola D . Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells. Oncotarget. 2015; 6(32):32821-40. PMC: 4741732. DOI: 10.18632/oncotarget.5104. View

3.
Brodeur G, Seeger R, Schwab M, Varmus H, Bishop J . Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984; 224(4653):1121-4. DOI: 10.1126/science.6719137. View

4.
Hogrebe A, von Stechow L, Bekker-Jensen D, Weinert B, Kelstrup C, Olsen J . Benchmarking common quantification strategies for large-scale phosphoproteomics. Nat Commun. 2018; 9(1):1045. PMC: 5849679. DOI: 10.1038/s41467-018-03309-6. View

5.
Takekoshi K, Nomura F, Isobe K, Motooka M, Nammoku T, Nakai T . Identification and initial characterization of stathmin by the differential display method in nerve growth factor-treated PC12 cells. Eur J Endocrinol. 1998; 138(6):707-12. DOI: 10.1530/eje.0.1380707. View