journal contribution
posted on 2023-03-31, 20:51 authored by Hai Huang, Chao Wang, Fei Liu, Hui-Zhen Li, Guang Peng, Xu Gao, Ke-Qin Dong, Hong-Ru Wang, De-Pei Kong, Min Qu, Li-He Dai, Kai-Jian Wang, Zhe Zhou, Jun Yang, Ze-Yu Yang, Yan-Qiong Cheng, Qin-Qin Tian, Dan Liu, Chuan-Liang Xu, Dan-Feng Xu, Xin-Gang Cui, Ying-Hao Sun Supplementary Figures and Figure Legends
Funding
National Natural Science Foundation of China
National Key Basic Research Program of China
Research Program of Science and Technology
Shanghai Municipal Health and Family Planning Commission
Shanghai Natural Science Foundation
Science and Technology Support
Zhangjiang National Innovation Demonstration Zone the National New Drug Innovation Program
Shanghai Clinical Medical Center for Urinary
History
ARTICLE ABSTRACT
Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via β-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612–26. ©2018 AACR.
