PUBLICATION
HDAC6 promotes growth, migration/invasion, and self-renewal of rhabdomyosarcoma
- Authors
- Pham, T.Q., Robinson, K., Xu, L., Pavlova, M.N., Skapek, S.X., Chen, E.Y.
- ID
- ZDB-PUB-201120-150
- Date
- 2020
- Source
- Oncogene 40(3): 578-591 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Neoplasm Invasiveness
- Humans
- Rhabdomyosarcoma/genetics
- Rhabdomyosarcoma/metabolism*
- Rhabdomyosarcoma/pathology
- Cell Movement*
- Histone Deacetylase 6/genetics
- Histone Deacetylase 6/metabolism*
- Cell Line, Tumor
- Cell Proliferation*
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism*
- PubMed
- 33199827 Full text @ Oncogene
Citation
Pham, T.Q., Robinson, K., Xu, L., Pavlova, M.N., Skapek, S.X., Chen, E.Y. (2020) HDAC6 promotes growth, migration/invasion, and self-renewal of rhabdomyosarcoma. Oncogene. 40(3):578-591.
Abstract
Rhabdomyosarcoma (RMS) is a devastating pediatric sarcoma. The survival outcomes remain poor for patients with relapsed or metastatic disease. Effective targeted therapy is lacking due to our limited knowledge of the underlying cellular and molecular mechanisms leading to disease progression. In this study, we used functional assays in vitro and in vivo (zebrafish and xenograft mouse models) to demonstrate the crucial role of HDAC6, a cytoplasmic histone deacetylase, in driving RMS tumor growth, self-renewal, and migration/invasion. Treatment with HDAC6-selective inhibitors recapitulates the HDAC6 loss-of-function phenotypes. HDAC6 regulates cytoskeletal dynamics to promote tumor cell migration and invasion. RAC1, a Rho family GTPase, is an essential mediator of HDAC6 function, and is necessary and sufficient for RMS cell migration and invasion. High expression of RAC1 correlates with poor clinical prognosis in RMS patients. Targeting the HDAC6-RAC1 axis represents a promising therapeutic option for improving survival outcomes of RMS patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping