Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027819 (
neuroblastoma
)
27,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Neuroblastoma
is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two
neuroblastoma
cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of
neuroblastoma
and the two tumors belong to the group of
neuroblastoma
exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and
ODZ4
. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in
neuroblastoma
. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in
neuroblastoma
oncogenesis.
...
PMID:Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. 2399 Oct 58
Teneurin-4
(
Ten-4
), a transmembrane protein, is highly expressed in the central nervous system; however, its cellular and molecular function in neuronal differentiation remains unknown. In this study, we aimed to elucidate the function of
Ten-4
in neurite outgrowth.
Ten-4
expression was induced during neurite outgrowth of the
neuroblastoma
cell line Neuro-2a.
Ten-4
protein was localized at the neurite growth cones. Knockdown of
Ten-4
expression in Neuro-2a cells decreased the formation of the filopodia-like protrusions and the length of individual neurites. Conversely, overexpression of
Ten-4
promoted filopodia-like protrusion formation. In addition, knockdown and overexpression of
Ten-4
reduced and elevated the activation of focal adhesion kinase (FAK) and Rho-family small GTPases, Cdc42 and Rac1, key molecules for the membranous protrusion formation downstream of FAK, respectively. Inhibition of the activation of FAK and neural Wiskott-Aldrich syndrome protein (N-WASP), which is a downstream regulator of FAK and Cdc42, blocked protrusion formation by
Ten-4
overexpression. Further,
Ten-4
colocalized with phosphorylated FAK in the filopodia-like protrusion regions. Together, our findings show that
Ten-4
is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the FAK signaling pathway.
...
PMID:Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling. 2434 32
