|Title:||Calreticulin mediates nerve growth factor-induced neuronal differentiation||Authors:||Shih Y.-Y.
|Issue Date:||2012||Journal Volume:||47||Journal Issue:||3||Start page/Pages:||571-581||Source:||Journal of Molecular Neuroscience||Abstract:||
The nerve growth factor (NGF)/TrkA-signaling is necessary for neural development, and its abnormality has been tightly associated with the tumorigenesis of various cancers originated from the nervous system. The characterization of key molecules involved in the NGF/TrkA-mediated neuronal differentiation could pave the way for the development of novel therapeutic strategies against neural malignancy. We have previously demonstrated that calreticulin (CRT) is a favorable prognostic factor highly expressed in primary neuroblastomas (NBs) with a more differentiated histology. In the present study, we found that the level of CRT was enhanced in NGF-stimulated differentiation of PC- 12 cells through the extracellular signal-regulated kinase (ERK)-dependent mitogen-activated protein kinase (MAPK)pathway. A deficiency of CRT significantly decreased NGF-elicited neuronal differentiation. Furthermore, overexpression of CRT enhanced neuronal differentiation via simultaneously activating the ERK-dependent MAPK pathway. The Ca2+-regulating capacity of CRT was demonstrated to be indispensable for NGF-elicited neuronal differentiation. Intriguingly, the expression levels of CRT and NGF receptor TrkA were highly correlated in NBs with differentiated histology, and the coexistence of CRT and TrkA in NB tumors synergistically predicted a better 5-year survival rate. Together, our present findings delineate a CRT-dependent regulation of NGF-induced neuronal differentiation. ? Springer Science+Business Media, LLC 2011.
|ISSN:||0895-8696||DOI:||10.1007/s12031-011-9683-3||SDG/Keyword:||antineoplastic agent; calcium ion; calreticulin; mitogen activated protein kinase; nerve growth factor; protein tyrosine kinase A; animal cell; article; autologous bone marrow transplantation; cancer chemotherapy; cancer patient; cancer radiotherapy; cell strain; cell viability; clinical trial; controlled study; gene overexpression; human; human cell; human tissue; immunohistochemistry; immunohistology; major clinical study; mediator; molecule; multimodality cancer therapy; nerve cell differentiation; neuroblastoma; nonhuman; protein analysis; protein expression; protein function; protein localization; protein protein interaction; signal transduction; survival rate; Western blotting; Animals; Calreticulin; Cell Differentiation; Nerve Growth Factor; Neurons; PC12 Cells; Rats; Receptor, trkA; Up-Regulation
|Appears in Collections:||解剖學暨細胞生物學科所|
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