Olfml2a Is Necessary For Anti-Triple Negative Breast Cancer Effect Of Selective Activator Protein-1 Inhibitor T-5224

Previous studies have shown that expression of activator protein-1 (AP-1) family is significantly elevated in triple negative breast cancer (TNBC), compared with that in other breast cancer subtypes. Here we investigated the antitumor effect and mechanism of T-5224, an inhibitor of c-Fos/AP-1, on TNBC. We identified that T-5224 inhibited the proliferation, migration, and invasion of TNBC cells and resulted in an increase in apoptosis. Furthermore, we found that OLFML2A is a key regulatory protein acting downstream of AP-1 and is involved in T-5224-targeted AP-1 action. Multiple clinical databases online have identified that high OLFML2A level is associated with poor prognosis in TNBC patients. In summary, our experimental and bioinformatic studies indicated that OLFML2A is necessary for AP-1-overexpressing TNBC. These findings demonstrate that AP-1-overexpressing TNBC dependent on OLFML2A, and targeting both AP-1 and OLFML2A through T -5224 may be a synergistic therapeutic strategy for this clinically challenging subset of breast cancer.