TY  - JOUR
AU  - Li, Peng
AU  - Lee, Eric H
AU  - Du, Fang
AU  - Gordon, Renata E
AU  - Yuelling, Larra W
AU  - Liu, Yongqiang
AU  - Ng, Jessica M Y
AU  - Zhang, Hao
AU  - Wu, Jinhua
AU  - Korshunov, Andrey
AU  - Pfister, Stefan
AU  - Curran, Tom
AU  - Yang, Zeng-Jie
TI  - Nestin Mediates Hedgehog Pathway Tumorigenesis.
JO  - Cancer research
VL  - 76
IS  - 18
SN  - 1538-7445
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2017-05051
SP  - 5573 - 5583
PY  - 2016
AB  - 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.
KW  - Gli3 protein, mouse (NLM Chemicals)
KW  - Hedgehog Proteins (NLM Chemicals)
KW  - Kruppel-Like Transcription Factors (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Nes protein, mouse (NLM Chemicals)
KW  - Nestin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27496710
C2  - pmc:PMC5091083
DO  - DOI:10.1158/0008-5472.CAN-16-1547
UR  - https://inrepo02.dkfz.de/record/129046
ER  -