Restore the brake on tumor progression

Gordon, Renata E.; Zhang, Li; Yang, Zeng-Jie

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Restore the brake on tumor progression

Supporting Files

Apr 05 2017
By Gordon, Renata E. ; Zhang, Li ; Yang, Zeng-Jie

File Language:

English

Details

Alternative Title:

Biochem Pharmacol
Personal Author:

Gordon, Renata E. ; Zhang, Li ; Yang, Zeng-Jie
Description:

Sonic hedgehog (Shh) signaling plays a key role in regulation of normal development. The negative feedback mechanism mediated by the transcriptional factor, Gli3, acts to finely tune Shh signaling, providing tight control of normal developmental processes. Hyperactivation of Shh signaling often leads to many human malignancies, including basal cell carcinoma and medulloblastoma (MB). However, how tumor cells sustain the aberrant activation of Shh signaling is still not completely understood. We recently revealed that during MB formation, tumor cells express Nestin, a type VI intermediate filament protein, which maintains uncontrolled Shh signaling by abolishing negative feedback by Gli3. Therefore, Nestin expression is a necessary step for MB formation. These findings highlight the novel function of Nestin in regulating Shh signaling, as well as the important role of a disrupted negative feedback mechanism in MB tumorigenesis. Further, restoration of the intrinsic negative feedback by repressing Nestin expression represents a promising approach to treat MB as well as other Shh signaling associated malignancies.
Subjects:

Animals Antineoplastic Agents Article Cerebellar Neoplasms Disease Progression Feedback, Physiological Hedgehog Proteins Humans Kruppel-Like Transcription Factors Medulloblastoma Models, Biological Molecular Targeted Therapy Neoplasm Proteins Nerve Tissue Proteins Nestin Signal Transduction Tumor Burden Zinc Finger Protein Gli3
Source:

Biochem Pharmacol. 138:1-6.
Pubmed ID:

28389227
Pubmed Central ID:

PMC5496785
Document Type:

Journal Article
Funding:

R01 CA178380/CA/NCI NIH HHS/United States ; R21 CA185504/CA/NCI NIH HHS/United States ; U50 DP424071/DP/NCCDPHP CDC HHS/United States
Volume:

138
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:fa444db5c892550501a0f503ab9001cc8bcc8fc591a8f993ffcbe646ec0f5696
Download URL:

https://stacks.cdc.gov/view/cdc/46589/cdc_46589_DS1.pdf
File Type:

[PDF - 420.73 KB ]

File Language:

English

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