Periplocin restores HTR1E signaling by CTCF to inhibit proliferation and dissemination of ovarian cancer

Ovarian cancer (OC) is one of the three malignant tumors threatening women's health, ranking third in incidence and second in mortality among all the gynaecological malignancies. The high mortality of OC is due to the lack of typical symptoms and effective early screening methods in the early stage. In the rapid progression of ovarian cancer, a risk factor that cannot be ignored and is currently a hot topic of cancer research is psychological stress. It is largely unknown about the key and robust factors directly linking psychological stress to the dissemination of cancer cells, causing the lack of effective intervening method. The dysregulation of the neurotransmitter 5-Hydroxytryptamine (5-HT) and its receptor HTR1E-mediated dissemination-suppressing function played an essential role in the growth and peritoneal dissemination of OC, indicating HTR1E to be a potential target for the prevention of the malignant progression of OC. In a previous systematic study screening Periplocin as monomer molecule isolated from the traditional Chinese medicine, it can effectivly restore the HTR1E expression and its anti-tumor signaling against the malignant growth and peritoneal disseminated metastasis of OC. We next found CTCF as insulator enforces TAD boundary between HTR1E and ZNF292 in cancer. CTCF is released from the boundary through competitive binding by Periplocin. In summary, we the first time identified Periplocin to be an effective natural small molecule that was able to restore the HTR1E expression and its anti-tumor signaling against the malignant growth and peritoneal disseminated metastasis of OC. We also clarified the molecular mechanism of the anti-tumor effects of Periplocin. This provides new evidence for the clinical treatment of ovarian cancer.