| First Author | Fukumoto T | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 13 | Pages | 3393-3400 |
| PubMed ID | 29590609 | Mgi Jnum | J:270936 |
| Mgi Id | MGI:6278344 | Doi | 10.1016/j.celrep.2018.03.019 |
| Citation | Fukumoto T, et al. (2018) Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer. Cell Rep 22(13):3393-3400 |
| abstractText | ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner. HDAC2 functions as a co-repressor of EZH2 to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse models. This correlated with a significant improvement of survival of mice bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers. |
