NUCB2/Nesfatin-1 drives breast cancer metastasis through the up-regulation of cholesterol synthesis via the mTORC1 pathway

• DOI: 10.1186/s12967-023-04236-x
• Publication Date: 2023-06-05T14:03:00Z
• Authors: Siyi Ning; Caiying Liu; Kangtao Wang; Yubo Cai; Zhicheng Ning; Ming Li; Liang Zeng
• Keywords: Research; Calcium-Binding Proteins; R; Breast Neoplasms; 3. Good health; Metastasis; Up-Regulation; DNA-Binding Proteins; Mice; Breast cancer; Cholesterol; Cholesterol synthesis; Medicine; Animals; Nucleobindins; Humans; Female; Nucleobindin-2/Nesfatin-1

Abstract Background Reprogramming lipid metabolism for tumor metastasis is essential in breast cancer, and NUCB2/Nesfatin-1 plays a crucial role regulating energy metabolism. Its high expression associated with poor prognosis cancer. Here, we studied whether promotes cancer through reprogramming cholesterol Methods ELISA was employed to measure the concentration of Nesfatin-1 serum patients control group. Database analysis suggested that might be acetylated which confirmed by treating cells acetyltransferase inhibitors. Transwell migration Matrigel invasion assays were conducted, nude mouse lung models established examine effect on vitro vivo. The Affymetrix gene chip results analyzed using IPA software identify critical pathway induced NUCB2/Nesfatin-1. We evaluated biosynthesis mTORC1-SREBP2-HMGCR axis utilizing mTORC1 inhibitor rescue experiments. Results found overexpressed patients, its overexpression positively correlated prognosis. NUCB2 potentially acetylated, leading promoted vivo, while rescued impaired cell depletion. Mechanistically, upregulated synthesis via signal pathway, contributing metastasis. Conclusions Our findings demonstrate NUCB2/Nesfatin-1/mTORC1/SREBP2 synthesis, Thus, utilized as diagnostic tool also used therapy future.