10.1158/0008-5472.CAN-16-1547 http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-16-1547 C5091083!5091083
!27496710
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Cancer+Res
2016 ; 76
(18
): 5573-83
Nephropedia Template TP gab.com Text Twit Text FOAVip Twit Text # English Wikipedia
Nestin Mediates Hedgehog Pathway Tumorigenesis
#MMPMID27496710
Li P
; Lee EH
; Du F
; Gordon RE
; Yuelling LW
; Liu Y
; Ng JM
; Zhang H
; Wu J
; Korshunov A
; Pfister SM
; Curran T
; Yang ZJ
Cancer Res
2016[Sep]; 76
(18
): 5573-83
PMID27496710
show ga
The intermediate filament protein Nestin serves as a biomarker for stem cells and
has been used to identify subsets of cancer stem-like cells. However, the
mechanistic contributions of Nestin to cancer pathogenesis are not understood.
Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3
to mediate the development of medulloblastomas of the hedgehog subtype. In a
mouse model system, Nestin levels increased progressively during medulloblastoma
formation, resulting in enhanced tumor growth. Conversely, loss of Nestin
dramatically inhibited proliferation and promoted differentiation. Mechanistic
investigations revealed that the tumor-promoting effects of Nestin were mediated
by binding to Gli3, a zinc finger transcription factor that negatively regulates
hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its
subsequent proteolytic processing, thereby abrogating its ability to negatively
regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog
pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these
malignancies. Cancer Res; 76(18); 5573-83. ©2016 AACR.
Please enable JavaScript to view the comments powered by Disqus. |Animals
[MESH] |Blotting, Western
[MESH] |Carcinogenesis
[MESH] |Cerebellar Neoplasms/metabolism/*pathology
[MESH] |Disease Models, Animal
[MESH] |Flow Cytometry
[MESH] |Hedgehog Proteins/*metabolism
[MESH] |Immunohistochemistry
[MESH] |Immunoprecipitation
[MESH] |Kruppel-Like Transcription Factors/*metabolism
[MESH] |Medulloblastoma/metabolism/*pathology
[MESH] |Mice
[MESH] |Microdissection
[MESH] |NIH 3T3 Cells
[MESH] |Nerve Tissue Proteins/*metabolism
[MESH] |Nestin/*metabolism
[MESH] |Oligonucleotide Array Sequence Analysis
[MESH] |Polymerase Chain Reaction
[MESH] DeepDyve Pubget Overpricing