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Eur J Cell Biol. 2016 Nov;95(11):465-474. doi: 10.1016/j.ejcb.2016.06.008. Epub 2016 Jun 24.

The TRPM7 interactome defines a cytoskeletal complex linked to neuroblastoma progression.

Author information

1
Laboratory of Pediatric Oncology, Radboud Institute for Molecular Life Sciences, Radboudumc, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
2
Division of Cell Biology I, The Netherlands Cancer Institute (NKI-AVL), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
3
Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboudumc, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Portland Square, Plymouth, PL4 8AA, UK.
4
Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
5
Laboratory of Pediatric Oncology, Radboud Institute for Molecular Life Sciences, Radboudumc, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Sygnature Discovery Limited, Biocity, Pennyfoot street, Nottingham, NG1 1GF, UK.
6
Laboratory of Pediatric Oncology, Radboud Institute for Molecular Life Sciences, Radboudumc, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: FrankN.vanLeeuwen@radboudumc.nl.

Abstract

Neuroblastoma is the second-most common solid tumor in children and originates from poorly differentiated neural crest-derived progenitors. Although most advanced stage metastatic neuroblastoma patients initially respond to treatment, a therapy resistant pool of poorly differentiated cells frequently arises, leading to refractory disease. A lack of insight into the molecular mechanisms that underlie neuroblastoma progression hampers the development of effective new therapies for these patients. Normal neural crest development and maturation is guided by physical interactions between the cell and its surroundings, in addition to soluble factors such as growth factors. This mechanical crosstalk is mediated by actin-based adhesion structures and cell protrusions that probe the cellular environment to modulate migration, proliferation, survival and differentiation. Whereas such signals preserve cellular quiescence in non-malignant cells, perturbed adhesion signaling promotes de-differentiation, uncontrolled cell proliferation, tissue invasion and therapy resistance. We previously reported that high expression levels of the channel-kinase TRPM7, a protein that maintains the progenitor state of embryonic neural crest cells, are closely associated with progenitor-like features of tumor cells, accompanied by extensive cytoskeletal reorganization and adhesion remodeling. To define mechanisms by which TRPM7 may contribute to neuroblastoma progression, we applied a proteomics approach to identify TRPM7 interacting proteins. We show that TRPM7 is part of a large complex of proteins, many of which function in cytoskeletal organization, cell protrusion formation and adhesion dynamics. Expression of a subset of these TRPM7 interacting proteins strongly correlates with neuroblastoma progression in independent neuroblastoma patient datasets. Thus, TRPM7 is part of a large cytoskeletal complex that may affect the malignant potential of tumor cells by regulating actomyosin dynamics and cell-matrix interactions.

KEYWORDS:

Cell adhesion; Cell protrusion; Cytoskeletal proteins; Neuroblastoma progression; TRPM7

PMID:
27402209
DOI:
10.1016/j.ejcb.2016.06.008
[Indexed for MEDLINE]

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