ETV4 interacts with LOXL2 to induce epigenetic activation of NID1 during colorectal cancer progression

作者：Tinghui Jiang, Xin Liu, Hao Liu, Kailong Du, Sen Wang, Hui Fan, Ying E. Zhang, Lin Cui, Hewei Zhang, Chun‐Dong Zhang, Yong Xia Zhu, Zhongyu Liu, Youquan Bu, Yunlong Lei · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.116383 · 被引用次数：2 · 研究领域：Microbial metabolism and enzyme function、Ferroptosis and cancer prognosis、Cancer-related gene regulation

. Mechanistic investigations found that LOXL2 was a novel transcriptional target and a direct interacting partner of ETV4 and was vital to ETV4-induced CRC malignant phenotypes. Further studies revealed that ETV4/LOXL2 complex could bind NID1 promoter to mediate its demethylation, induce NID1 expression and subsequent ERK signaling pathway activation, which is required for ETV4/LOXL2-mediated EMT and metastasis of CRC. Meanwhile, the expression of ETV4 and LOXL2 were significantly negatively correlated with the methylation of NID1 promoter in clinical samples. Besides, the combined ETV4, LOXL2 and NID1 as prognostic markers is more reliable than any one alone. Taken together, in this study, we demonstrated that ETV4 played a critical role in CRC metastasis, and unraveled the novel regulatory axis of ETV4/LOXL2/NID1, which contributed to the malignant progression of CRC.