OBJECTIVES: To investigate the effect of downregulation of medium-chain acyl-coenzyme A dehydrogenase (ACADM) on invasion and migration of estrogen receptor-positive breast cancer cells and the underlying mechanism. METHODS: The Kaplan-Meier Plotter database was used to analyze the ACADM expression levels in breast cancer and normal tissues and their association with patient prognosis. Human breast cancer MCF-7 and T47D cell lines with lentivirus-mediated ACADM knockdown were established, and their in situ tumor formation and metastasis after tail vein injection were evaluated in nude mice. The MCF-7 and T47D cells with ACADM knockdown and their unmodified parental cells were examined with oil-red O staining assay, ROS assay, mitochondrial respiratory chain function assay before and after treatments with ROS scavenger, Elamipretide (a cardiolipin oxidation inhibitor) or SC79 (an AKT activator), and the changes in migration and invasion abilities of the treated cells were analyzed with Transwell invasion assay and Boyden chamber assay. Western blotting was used to detect protein expression levels of related signaling pathways in the treated cells. RESULTS: ACADM overexpression was associated with a significantly shorter overall survival of breast cancer patients. In MCF-7 and T47D cells, ACADM knockdown resulted in downregulation of N calnexin, vimentin, p-P13K and p-AKT proteins, increased levels of free fatty acids and reactive oxygen species, lowered activities of mitochondrial respiratory chain complex III and V, and reduced mitochondrial inner phospholipids. ACADM knockdown significantly decreased the invasive capacity of the cells, which were obviously reversed by treatment with ROS scavenger, Elamipretide, and SC79. CONCLUSIONS Down-regulation of ACADM inhibits migration and invasion ability of estrogen receptor-positive breast cancer cells by lowering lipotoxicity and impairing mitochondrial function through the ROS/PI3K/AKT pathway.
Humans ; Breast Neoplasms/metabolism* ; Female ; Mice, Nude ; Down-Regulation ; Neoplasm Invasiveness ; Animals ; Mice ; Receptors, Estrogen/metabolism* ; MCF-7 Cells ; Cell Movement ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Acyl-CoA Dehydrogenase/genetics* ; Signal Transduction ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-akt/metabolism*

Treponema denticola is an important pathogenic Treponema pathogen in the human oral cavity. Early studies have found that Treponema denticola is closely related to the occurrence and development of periodontal diseases. With the development of technical methods in recent years, many studies have shown that Treponema denticola not only can participate in periodontal diseases through a variety of mechanisms but also can play an important role in the development of various oral diseases. Treponema denticola is detected in high concentrations in peri-apical diseases and peri-implant diseases, and its surface protein is also prevalent in oral tumor samples. This paper reviews the research progress of Treponema denticola in periodontal diseases, pulp peri-apical diseases, peri-implant diseases and oral tumors, and summarizes the relevant mechanisms. For example, Treponema denticola can cause immune regulation disorder, destroy the epithelial barrier, induce bone absorption, promote the occurrence and development of inflammation through a variety of surface proteins, including chymotrypsin-like protease complex (CTLP), major outer sheath protein (Mosp), Td92, and LOS. It can also escape complement-mediated killing effects through surface FhbB lipoproteins and promote the occurrence and development of oral tumors by regulating the tumor microenvironment. These theories provide a theoretical basis for further understanding the development of oral diseases, controlling the infection of Treponema denticola, and exploring more effective treatment strategies.