Elucidating the proteomic characteristics and metabolic pathway activation in breast cancer bone metastasis
10.12354/j.issn.1000-8179.2024.20240410
- VernacularTitle:乳腺癌骨转移的蛋白质组学特性及代谢途径活化研究
- Author:
Yuan CHUNLU
1
;
Chen LONG
;
Liao YAFANG
;
Shi JIANUO
;
Zhang DANDAN
Author Information
1. 上海中医药大学交叉科学研究院(上海市 201203)
- Keywords:
breast cancer bone metastasis;
proteomics;
S100 calcium-binding protein A(S100A4);
tumor metabolism;
signaling path-ways
- From:
Chinese Journal of Clinical Oncology
2024;51(13):695-702
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protein expression characteristics of bone metastatic breast cancer cells and the underlying molecu-lar mechanism driving bone metastasis.Methods:A firefly luciferase-overexpressing human breast cancer cell line,MCF-7-luc,and its bone metastasis subline,MCF-7-BOM-luc,were established.Additionally,a nude mouse model of breast cancer bone metastasis was established by injecting the aforementioned cells into the left ventricle.Bone metastasis and trabecular changes were assessed using micro-computed tomography(Micro-CT).Cell migration,and invasion were evaluated using the Transwell assays.Differential protein expression and epithelial-mesenchymal transition(EMT)were analyzed using proteomics,Western blot,and reverse transcription-quantitative PCR(qPCR).We meas-ured the glucose uptake,L-lactic acid content,and cell energy metabolism parameters using 2-NBDG,ELISA,and a Seahorse energy metabol-izer.Results:MCF-7-BOM-luc cells exhibited stronger migration,invasion,and EMT characteristics as well as more pronounced bone meta-stasis capabilities than the MCF-7-luc cells.Proteomic analysis revealed increased S100 calcium-binding protein A(S100A4)expression in MCF-7-BOM-luc cells,with other differentially expressed proteins being primarily involved in metabolic pathways.Additionally,MCF-7-BOM-luc cells displayed increased expression of E-box binding homeobox 1/2(zinc finger E-box binding homeobox 1/2,ZEB1/2)and Vimentin and reduced E-cadherin expression.MCF-7-BOM-luc cells also exhibited enhanced glucose uptake,L-lactic acid production,and glycolysis rates as well as increased phosphorylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)and signal transducer and activator of tran-scription 3(STAT3).Conclusions:MCF-7-BOM-luc cells promote S100A4 expression through ERK1/2 and STAT3 signaling pathway activation,which in turn enhances the EMT process and glycolysis rate,thereby contributing to malignant bone metastasis.Proteomic analysis of breast cancer bone metastasis-related protein characteristics could offer potential targets for the diagnosis,prevention,and treatment of breast cancer bone metastasis.
