RANK Signaling Blockade Reduces Breast Cancer Recurrence by Inducing Tumor Cell Differentiation.

摘要: RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remains unknown. RANKL and receptor are downstream effectors of the progesterone signaling pathway. However, enriched hormone negative adenocarcinomas, suggesting additional roles for beyond hormone-dependent function. Here, to explore role once tumors have developed, we use mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT), which mimics patterns seen human adenocarcinomas. Complementary genetic pharmacologic approaches demonstrate that inhibition drastically reduces stem cell pool, decreases metastasis initiation, enhances sensitivity chemotherapy. Mechanistically, genome-wide analyses show anti-RANKL therapy promotes lactogenic differentiation cells. Moreover, cells negatively regulates Ap2 transcription factors, Wnt agonist Rspo1 Sca1-population, tumor-initiating In addition, found TFAP2B inhibitor, OPG, correlate relapse-free tumors. These results support inhibitors reduce recurrence patients based on ability induce differentiation. Cancer Res; 76(19); 5857–69. ©2016 AACR.