| First Author | Bartholf DeWitt S | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 17 | PubMed ID | 36073547 |
| Mgi Jnum | J:329449 | Mgi Id | MGI:7344912 |
| Doi | 10.1172/jci.insight.151583 | Citation | Bartholf DeWitt S, et al. (2022) Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-kappaB signaling and integrin binding. JCI Insight 7(17):e151583 |
| abstractText | Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-kappaB signaling, extracellular matrix remodeling, increased integrin alphavbeta3 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-kappaB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X alpha thalassemia intellectual disability syndrome. |
