| Title | RGFP966, a histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Liang H, Wang Q, Wang D, Zheng H, Kalvakolanu DV, Lu H, Wen N, Chen X, Xu L, Ren J, Guo B, Zhang L |
| Journal | Biochem Pharmacol |
| Volume | 180 |
| Pagination | 114118 |
| Date Published | 2020 10 |
| ISSN | 1873-2968 |
| Keywords | Acrylamides, Animals, Brain Neoplasms, Cell Differentiation, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, Glioma, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplastic Stem Cells, Phenylenediamines, RNA, Small Interfering, Signal Transduction, Smad7 Protein, Transforming Growth Factor beta, Xenograft Model Antitumor Assays |
| Abstract | Glioma stem cells (GSC) play a major role in drug resistance and tumor recurrence. Using a genetic screen with a set of shRNAs that can target chromatin regulators in a GSC model, we have HDAC3 as a major negative regulator of GSC differentiation. Inhibition of HDAC3 using a pharmacological inhibitor or a siRNA led to the induction of GSC differentiation into astrocytes. Consequently, HDAC3-inhibition also caused a strong reduction of tumor-promoting and self-renewal capabilities of GSCs. These phenotypes were highly associated with an increased acetylation of SMAD7, which protected its ubiquitination. SMAD7 inhibits a TGF-β signaling axis that is required for maintaining stemness. These results demonstrate that HDAC3 appears to be a proper target in anti-glioma therapy. |
| DOI | 10.1016/j.bcp.2020.114118 |
| Alternate Journal | Biochem Pharmacol |
| PubMed ID | 32585142 |
Related Faculty:
Hongwu Zheng, Ph.D.