LSD1 deficiency in breast cancer cells promotes the formation of pre-metastatic niches
Year: 2024
Type: article
Abstract: Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. Studies show LSD1 knockout promotes breast cancer lung metastasis, but it's unknown if it alters the lung microenvironment for metastasis. In this study, we investigated the effects of exosomes from LSD1-knockdown (LSD1 KD) breast cancer cells on pre-metastatic niche formation. Injecting exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the ZO-1 and occludin, leading to increased vascular permeability. The LSD1 KD reduced the expression of circDOCK1, which augmented the levels of miR-1270 in exosomes. And miR-1270 inhibited ZO-1 expression in human endothelial cells, which enhanced their permeability. Our study uncovered a novel mechanism in which the LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA.
Source: npj Precision Oncology
Authors: Yutong Yao, Rui Qian, Hanwei Gao, Yonghao Dai, Yueru Shi, Peipei An, Benkai Xin, Ziyu Liu, Nan Zhang, Youzhong Wan, Yuquan He, Xin Hu
Institution: Jilin University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
Awards: G6546781788, G8411271755
OpenAlex ID: W4404233629