Enhancer reprogramming promotes the activation of cancer-associated fibroblasts and breast cancer metastasis
Qian Li, Xuejiao Lv, Chunyong Han, Yu Kong, Zhongye Dai, Dawei Huo, Ting Li, Dapeng Li, Wei Li, Xing Wang, Qian Zhao, Jie Ming, Wen Yang, Yang Chen, Xudong Wu
Abstract
Rationale: Cancer associated fibroblasts (CAFs) are a subpopulation of cells within the tumor microenvironment that usually promote cancer progression and metastasis. Hence it is critical to find out the driving factors and mechanisms for the development of CAFs from normal fibroblasts (NFs) in response to sustained stimulation of cancer cells. Here we perform transcriptomic and epigenomic analyses in paired NFs and CAFs associated with breast cancer metastasis to investigate the molecular mechanisms for stromal fibroblasts reprogramming. Methods: We conducted transcriptomic analyses in paired NFs and CAFs isolated from clinical specimens of breast cancer patients with metastasis. Meanwhile, genome-wide mapping of histone marks H3K4me1 and H3K27ac was also performed to characterize CAF-specific enhancer landscape. The function and mechanisms of activated JUN in stromal fibroblasts were studied using in vitro and in vivo models.