HDAC6 promotes growth, migration/invasion, and self-renewal of rhabdomyosarcoma

Thao Q. Pham, Kristin Robinson, Lin Xu, Maria N. Pavlova, Stephen X. Skapek, Eleanor Y. Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)578-591
Number of pages14
JournalOncogene
Volume40
Issue number3
DOIs
StatePublished - Jan 21 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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