TY - JOUR TI - Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer AU - Zhang, Baotong AU - Li, Yixiang AU - Wu, Qiao AU - Xie, Lin AU - Barwick, Benjamin AU - Fu, Changying AU - Li, Xin AU - Wu, Daqing AU - Xia, Siyuan AU - Chen, Jing AU - Qian, Wei Ping AU - Yang, Lily AU - Osunkoya, Adeboye O. AU - Boise, Lawrence AU - Vertino, Paula M. AU - Zhao, Yichao AU - Li, Menglin AU - Chen, Hsiao-Rong AU - Kowalski, Jeanne AU - Kucuk, Omer AU - Zhou, Wei AU - Dong, Jin-Tang T2 - Nature Communications AB - Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling. DA - 2021/03/17/ PY - 2021 DO - 10.1038/s41467-021-21976-w DP - www.nature.com VL - 12 IS - 1 SP - 1714 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-21976-w Y2 - 2021/03/17/21:06:57 ER -