NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C
(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 mole...
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2021
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oai:doaj.org-article:ccae7d8193394cd68660886cb97372272021-11-11T15:27:28ZNTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C10.3390/cancers132152932072-6694https://doaj.org/article/ccae7d8193394cd68660886cb97372272021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5293https://doaj.org/toc/2072-6694(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.Lukas FunkeThilo BrachtSebastian OeckKarin SchorkMarkus StepathSabine DreesmannMartin EisenacherBarbara SitekAlexander SchrammMDPI AGarticlephosphoproteomicsmass spectrometryphosphorylationproteomicsMYCNnuclear fociNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5293, p 5293 (2021) |
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phosphoproteomics mass spectrometry phosphorylation proteomics MYCN nuclear foci Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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phosphoproteomics mass spectrometry phosphorylation proteomics MYCN nuclear foci Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lukas Funke Thilo Bracht Sebastian Oeck Karin Schork Markus Stepath Sabine Dreesmann Martin Eisenacher Barbara Sitek Alexander Schramm NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
description |
(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. |
format |
article |
author |
Lukas Funke Thilo Bracht Sebastian Oeck Karin Schork Markus Stepath Sabine Dreesmann Martin Eisenacher Barbara Sitek Alexander Schramm |
author_facet |
Lukas Funke Thilo Bracht Sebastian Oeck Karin Schork Markus Stepath Sabine Dreesmann Martin Eisenacher Barbara Sitek Alexander Schramm |
author_sort |
Lukas Funke |
title |
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
title_short |
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
title_full |
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
title_fullStr |
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
title_full_unstemmed |
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C |
title_sort |
ntrk1/trka signaling in neuroblastoma cells induces nuclear reorganization and intra-nuclear aggregation of lamin a/c |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/ccae7d8193394cd68660886cb9737227 |
work_keys_str_mv |
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