Molecular Mechanism Of ACADM Enhancing Malignant Biological Behavior Of Estrogen Receptor-positive Breast Cancer

Background and PurposeBreast cancer is one of the most common malignant tumors in women.At least 400,000 women die of breast cancer every year.Tumor invasion and metastasis are still the main causes of most malignant tumor-related deaths,especially primary or secondary drug resistance.Post-recurrence and metastasis are urgently needed to find new targets for treatment to improve the quality of life and prolong survival of breast cancer patients.Our group’s previous experiments screened one of the possible interacting proteins with mitogen-activated protein kinase 4(MAP2K4),a medium chain acyl-CoA dehydrogenase(ACADM),which catalyzes the fatty acyl-CoA in mitochondria.The first dehydrogenation step of β-oxidation,the lack of ACADM in neonates will lead to hereditary mitochondrial fatty acid oxidation disorders.However,ACADM has rarely been reported in tumors,and little is known about its role and molecular mechanism.This article will focus on the relationship between ACADM and breast cancer,identify its role in breast cancer,explore its function,and analyze its specific molecular mechanism of action,in order to provide new therapeutic targets for further diagnosis and treatment of breast cancer.Methods1.Transient transfection and transfection of lentivirus to increase the protein expression of the target gene,and verify the transfection efficiency by real-time quantitative PCR(RT-PCR)or Western Blot.2.MTT,EdU,Transwell chamber migration,Boyden in vitro invasion experiments and other in vitro functional experiments to verify the proliferation,invasion and migration of breast cancer cells.3.Western Blot detects the expression of related pathway protein and explores the molecular mechanism of the target gene.Results1.Database analysis showed that AC ADM had significant statistical differences in the expression of cancer tissues and normal tissues.2.Establish a breast cancer cell line stably expressing ACADM.3.AC ADM can promote the invasion,migration and proliferation of breast cancer MCF-7 and T47D cells in vitro,but has no significant effect on the invasion,migration and proliferation of SKBR3 and MDA-MB-231.4.The ability of breast cancer cells to invade and migrate in vitro after interference with silencing ACADM expression decreased.5.After overexpression of ACADM,ER and FASN expression were up-regulated.6.ESR1 can further promote ACADM to enhance cell invasion and migration,and up-regulate ACADM and FASN expression.7.FASN is downstream of ACADM and ESR1.After interfering with FASN expression,the migration and invasion ability of breast cancer cells decreased.8.ACADM and ESR1 regulate FASN through PI3K/AKT pathway to enhance the molecular mechanism of breast cancer cell migration and invasion.9.The effect of different concentrations of metformin on migration and invasion of MCF-7 cells overexpressing ACADM.Conclusion:ACADM and ESR1 synergistically enhance the migration and invasion of estrogen receptor-positive breast cancer cells by activating PI3K/AKT pathway to regulate FASN...